• HIV pathogenesis
• VNP
• natural SIV host
• pediatric HIV infection
• viremic non-progressor

• Humans
• Simian Immunodeficiency Virus/physiology
• Simian Acquired Immunodeficiency Syndrome/immunology
• Simian Acquired Immunodeficiency Syndrome/virology
• HIV Infections/immunology
• HIV Infections/virology
• HIV Infections/drug therapy
• HIV Infections/pathology
• Animals
• Viremia/immunology
• Viremia/virology
• Disease Progression
• Viral Load
• CD4-Positive T-Lymphocytes/immunology
• Host-Pathogen Interactions/immunology
• HIV-1

• CD4 T cells
• Candida albicans
• Langerhans cells
• MHC-II antigen presentation
• T cytotoxic 17 cells (Tc17)
• oral mucosa

• R01 DE030095 NIDCR NIH HHS
• R21 DE029289 NIDCR NIH HHS
• R21 DE029601 NIDCR NIH HHS

• AIDS
• HIV
• Immune reconstitution
• Mucosal immunity
• Mucosal-associated invariant T cells

• Epithelial barrier disruption
• Jejunum
• Mitochondrial dysfunction
• Reactive oxygen species
• SIV infection

• Animals
• Humans
• Hydrogen Peroxide
• Intestinal Mucosa
• Macaca mulatta
• Reactive Oxygen Species
• Simian Acquired Immunodeficiency Syndrome
• Simian Immunodeficiency Virus

As one of the subsets of CD8⁺ T cells, Tc17 cells have recently been identified and are characterized by the secretion of interleukin (IL)-17, which is related to inflammatory diseases.

To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer development.

Flow cytometry assay, immunohistochemistry, and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical cancer. Prior to cell suspension culture, ELISA was carried out to measure the production of IL-6, IL-1β, IL-23, CXCL12, and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical cancer. In addition, multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model.

Compared with normal tissues, Tc17 cells specifically accumulated in tumor tissues of cervical cancer patients. Cancer cells produced a greater amount of IL-6, IL-1β, and IL-23, which in turn promoted Tc17 cell polarization. Unlike the traditional cytotoxic CD8⁺ T cells, Tc17 cells secreted IL-17, which subsequently promoted CXCL12 expression in tumor cells, eventually enhancing the proliferation and migration of tumor cells. Thus, the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical cancer.

Our data identified the oncogenic role of Tc17 cells in the development of cervical cancer. We propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.

• Cervical cancer
• Tc17 cells
• Interleukin-17
• Cancer development
• Biological function
• Oncogenic role

• CD8+ T-cell
• CXCR5
• HIV
• IL-17
• antiretroviral therapy
• exhaustion

• mucosal immunology
• hiv infections

• Adolescent
• Adult
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/metabolism
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/metabolism
• Case-Control Studies
• Cohort Studies
• HIV/immunology
• HIV/metabolism
• HIV Infections/immunology
• HIV Infections/metabolism
• HIV Infections/virology
• Humans
• Interleukin-17/metabolism
• Leukocytes, Mononuclear/immunology
• Leukocytes, Mononuclear/metabolism
• Male
• Middle Aged
• Mucous Membrane/immunology
• Mucous Membrane/metabolism
• T-Lymphocyte Subsets/immunology
• T-Lymphocyte Subsets/metabolism
• T-Lymphocytes, Cytotoxic/immunology
• Young Adult

• P30 AI050409 NIAID NIH HHS
• R01 GM116065 NIGMS NIH HHS
• P51 OD011132 NIH HHS
• R01GM116065 U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
• P01 AI088575 NIAID NIH HHS
• T32 DK108735 NIDDK NIH HHS
• K23 AI108335 NIAID NIH HHS
• R01 HD092033 NICHD NIH HHS
• UL1 TR000454 NCATS NIH HHS
• U19 AI109633 NIAID NIH HHS
• AI128799 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
• UL1TR000454 U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)
• U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
• U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
• U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
• U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)

Purinergic signaling modulates systemic and local inflammatory responses. Extracellular nucleotides, including eATP, promote inflammation, at least in part via the inflammasome upon engagement of P2 purinergic receptors. In contrast, adenosine generated during eATP phosphohydrolysis by ectonucleotidases, triggers immunosuppressive/anti-inflammatory pathways. Mounting evidence supports the role of ectonucleotidases, especially ENTPD1/CD39 and CD73, in the control of several inflammatory conditions, ranging from infectious disease, organ fibrosis to oncogenesis. Our experimental data generated over the years have indicated both CD39 and CD73 serve as pivotal regulators of intestinal and hepatic inflammation. In this context, immune cell responses are regulated by the balance between eATP and adenosine, potentially impacting disease outcomes as in gastrointestinal infection, inflammatory bowel disease, ischemia reperfusion injury of the bowel and liver, autoimmune or viral hepatitis and other inflammatory conditions, such as cancer. In this review, we report the most recent discoveries on the role of ENTPD1/CD39, CD73, and other ectonucleotidases in the regulation of intestinal and hepatic inflammation. We discuss the present knowledge, highlight the most intriguing and promising experimental data and comment on important aspects that still need to be addressed to develop purinergic-based therapies for these important illnesses.

• ATP
• T-cell
• adenosine
• ectonucleotidase
• intestine
• liver

• Th17
• Treg
• antiretroviral therapy
• mucosal immune responses
• rhesus macaque
• simian immunodeficiency virus

• CD2
• CD58
• SIV
• cytokine
• mucosal immunology

Immune activation is the hallmark of HIV infection, even in patients with highly active anti-retroviral therapy (HAART)-induced viral suppression. A major cause of immune activation during HIV infection is the intestinal microbial translocation as a consequence, among other factors, of the decrease and/or dysfunction of interleukin (IL)-17-producing T-cells, due to their role promoting the integrity of the intestinal barrier. A population of IL-17-producing CD8⁺ T-cells (Tc17 cells), characterized by the expression of CD161, has been described, but its relation with the persistent immune activation in non-viremic people living with HIV (PLWH) on HAART is unclear. By flow cytometry, we characterized the activation phenotype (evaluated by the expression of HLA-DR and CD38) of circulating CD161-expressing CD8⁺ T-cells; in addition, we explored the functionality of polyclonally-stimulated Tc17 cells in PLWH under HAART-induced viral suppression, and in healthy individuals. Finally, we determined the association of Tc17 cells with the expression of cellular and soluble activation markers. Circulating CD161-expressing CD8⁺ T-cells were decreased in PLWH compared with healthy individuals, despite their similar basal activation state. After polyclonal stimulation, IL-17 production was higher in CD8⁺ T-cells co-expressing HLA-DR and CD38 in healthy individuals. In contrast, although PLWH had a higher frequency of HLA-DR⁺ CD38⁺ CD8⁺ T-cells after stimulation, they had a lower production of IL-17. Interferon (IFN)-γ-producing CD8⁺ T-cells (Tc1 cells) were increased in PLWH. The low Tc17 cells response was associated with a high expression of CD38 and programmed death 1 protein, high levels of soluble CD14 and the treatment duration. Finally, to explore potential immunomodulatory strategies, the in vitro effect of the anti-inflammatory agent sulfasalazine was assessed on Tc17 cells. Interestingly, a decreased inflammatory environment, death of activated CD8⁺ T-cells, and an increased frequency of Tc17 cells were observed with sulfasalazine treatment. Thus, our findings suggest that activated CD8⁺ T-cells have a marked capacity to produce IL-17 in healthy individuals, but not in PLWH, despite HAART. This dysfunction of Tc17 cells is associated with the persistent immune activation observed in these patients, and can be partially restored by anti-inflammatory agents.

• CD161
• CD8+ T cells
• HAART
• HIV
• IL-17
• sCD14
• sulfasalazine

• antineoplastic agent
• immunocompromised host
• immunosuppression
• mycosis fungoides
• peripheral tolerance
• pregnancy
• programmed cell death 1 protein

• GALT
• GUT
• HIV-1
• HSP60
• IELs
• T-cell activation
• Tc1
• Tc17
• Th1
• Th17
• apoptosis
• immunity
• probiotics

• Adult
• Anti-Retroviral Agents/administration & dosage
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/pathology
• HIV Seropositivity/drug therapy
• HIV Seropositivity/immunology
• HIV Seropositivity/pathology
• HIV-1/immunology
• Humans
• Intestinal Mucosa/immunology
• Intestinal Mucosa/pathology
• Lymphocyte Activation/drug effects
• Male
• Middle Aged
• Mitochondria/immunology
• Mitochondria/pathology
• Probiotics/administration & dosage
• Th1 Cells/immunology
• Th1 Cells/pathology
• Th17 Cells/immunology
• Th17 Cells/pathology

During HIV infection, specific responses exhibited by CD8⁺ T cells are crucial to establish an early, effective, and sustained viral control, preventing severe immune alterations and organ dysfunction. Several CD8⁺ T cells subsets have been identified, exhibiting differences in terms of activation, functional profile, and ability to limit HIV replication. Some of the most important CD8⁺ T cells subsets associated with viral control, production of potent antiviral molecules, and strong polyfunctional responses include Th1-like cytokine pattern and Tc17 cells. In addition, the expression of specific activation markers has been also associated with a more effective response of CD8⁺ T cells, as evidenced in HLA-DR⁺ CD38⁻ cells. CD8⁺ T cells in both, peripheral blood and gut mucosa, are particularly important in individuals with a resistant phenotype, including HIV-exposed seronegative individuals (HESNs), long-term non-progressors (LTNPs) and HIV-controllers. Although the role of CD8⁺ T cells has been extensively explored in the context of an established HIV-1 infection, the presence of HIV-specific cells with effector abilities and a defined functional profile in HESNs, remain poorly understood. Here, we reviewed studies carried out on different subpopulations of CD8⁺ T cells in relation with natural resistance to HIV infection and progression.

• CD8+ T cells subpopulations
• HIV infection
• antiviral immune response
• natural resistance to HIV
• spontaneous control of HIV replication

The interleukin-17 (IL-17) family cytokines, such as IL-17A and IL-17F, play important protective roles in host immune response to a variety of infections such as bacterial, fungal, parasitic, and viral. The IL-17R signaling and downstream pathways mediate induction of proinflammatory molecules which participate in control of these pathogens. However, the production of IL-17 can also mediate pathology and inflammation associated with infections. In this review, we will discuss the yin-and-yang roles of IL-17 in host immunity to pathogens.

• IL-17
• host immune response
• pathogens

In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against wild-type SIVmac239. Indian rhesus macaques were vaccinated either with SIVrtTA or with SIVmac239Δnef. Doxycycline was withdrawn from 4 of 8 SIVrtTA vaccinates before challenge with wild-type virus. Unvaccinated challenge controls exhibited ~10⁷ peak plasma viral RNA copies/ml persisting beyond the acute phase. Six vaccinates, four SIVmac239Δnef and two SIVrtTA vaccinates exhibited complete protection, defined by lack of wild-type viraemia post-challenge and virus-specific PCR analysis of tissues recovered post-mortem, whereas six SIVrtTA vaccinates were protected from high levels of viraemia. Critically, the complete protection in two SIVrtTA vaccinates was associated with enhanced SIVrtTA replication in the immediate post-acute vaccination period but was independent of doxycycline status at the time of challenge. Mutations were identified in the LTR promoter region and rtTA gene that do not affect doxycycline-control but were associated with enhanced post-acute phase replication in protected vaccinates. High frequencies of total circulating CD8⁺T effector memory cells and a higher total frequency of SIV-specific CD8⁺ mono and polyfunctional T cells on the day of wild-type challenge were associated with complete protection but these parameters were not predictive of outcome when assessed 130 days after challenge. Moreover, challenge virus-specific Nef CD8⁺ polyfunctional T cell responses and antigen were detected in tissues post mortem in completely-protected macaques indicating post-challenge control of infection. Within the parameters of the study design, on-going occult-phase replication may not be absolutely required for protective immunity.

Development of an HIV vaccine remains a global health priority. In non-human primates live-attenuated SIV induces a potent vaccine effect. Following disappearance of vaccine virus from the peripheral circulation replication persists in lymphoid tissue. To address whether this occult replication is critical to the generation of protective immunity we used a novel construct (SIVrtTA) based on the prototypic live attenuated SIVmac239Δnef but which requires the presence of the antibiotic doxycycline to replicate. Protection appeared independent of doxycycline status at the time of virulent virus challenge suggesting that occult replication may not be absolutely necessary for persistence of immunity; however, stronger protection was observed in monkeys vaccinated with SIVrtTA where vaccine replication persisted for longer after peak viraemia. Moreover, some evidence of very low level breakthrough of vaccine virus replication was seen and protection was weaker than that obtained with SIVmac239Δnef. Both vaccination and challenge perturbed circulating T cell populations, but only the frequency of SIV-specific CD8⁺ polyfunctional T cells measured on the day of challenge was associated with protection. Replication-conditional mutants such as SIVrtTA have great potential in unlocking the complex interactions between the vaccine virus and host responses in the generation of potent anti-viral protection in vivo.

• Animals
• Immunohistochemistry
• Immunophenotyping
• Macaca mulatta
• Polymerase Chain Reaction
• SAIDS Vaccines/immunology
• Simian Acquired Immunodeficiency Syndrome/immunology
• Simian Immunodeficiency Virus/immunology
• Vaccines, Attenuated
• Virus Replication/immunology

• G0600007 Medical Research Council
• G0601201 Medical Research Council
• G9025730 Medical Research Council
• IAVI

• gut-homing
• hiv-1 disease pathogenesis
• integrin α4β7
• th17 cells

• Acute Disease
• Adolescent
• Adult
• CD4-Positive T-Lymphocytes/metabolism
• HIV Infections/immunology
• Humans
• Integrins/metabolism
• Lymphocyte Depletion
• Lymphocyte Subsets/metabolism
• Middle Aged
• T-Lymphocytes, Regulatory/immunology
• Th1 Cells/immunology
• Th17 Cells/immunology
• Young Adult

Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

Chronic immune activation is a hallmark of HIV infection and contributes in multiple ways to HIV persistence. Here, we gained insights on the association between a pro-inflammatory chemokine, CXCL10/IP-10 and HIV infection in four cohorts of HIV+ individuals, studied at distinct stages of infection (before, primary and chronic stage with spontaneous- and treatment-controlled infection). We further analyzed pathogenic and non-pathogenic SIV infections to address IP-10 levels and the presence of infected cells in tissues (lymph nodes, small and large intestine). We found that elevated systemic IP-10 levels before HIV-1 infection associate with a more rapid disease progression. During primary infection, IP-10 in blood strongly correlated with the amount of infected cells in blood. The animal model showed that IP-10 expression was regionalized in the intestine and highest in the small intestine. Studies of aviremic animals suggest that high IP-10 is indicative of viral replication in lymphoid tissues. Haematopoietic cells rather than epithelial/endothelial cells mainly contributed to the IP-10 production in small intestine (jejunum). The receptor of IP-10 was highly expressed on memory CD4+ T cells, i.e. major target cells for the virus. This study contributes to our understanding of the establishment of HIV reservoirs and why IP-10 associates with HIV/AIDS.

• Bacterial loads
• Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV)
• Infection
• Lung
• Piglets
• Suppression
• Th17 cells

• Gut barrier integrity
• HIV
• Interleukin-21
• Interleukin-7
• Microbial translocation
• SIV

Fungal infections have skyrocketed in immune-compromised patients lacking CD4⁺ T cells, underscoring the need for vaccine prevention. An understanding of the elements that promote vaccine immunity in this setting is essential. We previously demonstrated that vaccine-induced IL-17A⁺ CD8⁺ T cells (Tc17) are required for resistance against lethal fungal pneumonia in CD4⁺ T cell-deficient hosts, whereas the individual type I cytokines IFN-γ, TNF-α and GM-CSF, are dispensable. Here, we report that T cell-intrinsic MyD88 signals are crucial for these Tc17 cell responses and vaccine immunity against lethal fungal pneumonia in mice. In contrast, IFN-γ⁺ CD8⁺ cell (Tc1) responses are largely normal in the absence of intrinsic MyD88 signaling in CD8⁺ T cells. The poor accumulation of MyD88-deficient Tc17 cells was not linked to an early onset of contraction, nor to accelerated cell death or diminished expression of anti-apoptotic molecules Bcl-2 or Bcl-xL. Instead, intrinsic MyD88 was required to sustain the proliferation of Tc17 cells through the activation of mTOR via Akt1. Moreover, intrinsic IL-1R and TLR2, but not IL-18R, were required for MyD88 dependent Tc17 responses. Our data identify unappreciated targets for augmenting adaptive immunity against fungi. Our findings have implications for designing fungal vaccines and immune-based therapies in immune-compromised patients.

Patients with AIDS, cancer or immune suppressive treatments are vulnerable to infection with invasive fungi. We have found that even when helper CD4 T cells are profoundly reduced in a mouse model that mimics this defect in AIDS, other remaining T cells are capable of mounting vaccine immunity against a deadly fungal infection, and they do so by producing the powerful, soluble product, IL-17. It has been widely believed that the activation and instruction of such cells, called Tc17 cells, is governed by another population of immune cells in the body, but we have found here that pathways within these Tc17 cells themselves mediate their activation and ability to produce the IL-17 needed for resistance to infection. We have also identified elements of the circuitry controlling this pathway—elements called MyD88, Akt1 and mTOR—and found that they control the production of IL-17 and not other products such as IFN-γ often produced by these cells. Further, we determined that this circuitry controls the development of Tc17 cells by regulating their ability to divide and expand. Thus, in a mouse model of vaccination against lethal fungal pneumonia caused by Blastomyces dermatitidis, we uncovered an important cellular arsenal that can be recruited to bolster resistance against a fungal infection, and identified novel ways in which the cells develop and expand into potent killers of fungi.

The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate defences in the intestinal mucosa during HIV-1 infection has not been well characterized. This study examined the frequency, phenotype, and functional status of T cell populations in the gut-associated lymphoid tissue and peripheral blood of virologically suppressed HIV-1-infected patients on therapy, focusing on the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell activation (CD38 and HLADR expression) into the GALT despite the higher levels of Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN response in GALT compared to the peripheral blood compartment was also recorded. Furthermore, IFN-α/β levels were negatively related to the frequencies of Th1 naïve cells and Tc1 cell subsets (naïve, central memory, and effector memory) in the GALT. In contrast, no relationships between type I IFN response and Th1 or Tc1 cell subsets in peripheral blood compartment and between IFN-α/β and Th17/Tc17 in both GALT and peripheral blood district were recorded. These data indicate that prolonged antiretroviral treatment improves GALT immune function despite the persistence of immune activation and type I IFN response in chronic HIV-1 positive patients.

• AIDS
• Chagas disease
• HIV
• Immunohistochemical
• Reactivation

• Endometrial carcinoma
• Tc17
• Th17
• Treg
• Tumor immunity

The past decade has seen the emergence of innate immunity as a mature field. The study of innate immunity has had a significant impact on the concepts of HIV immunity, pathogenesis, and vaccines. In this chapter, basic concepts of innate immunity at the anatomical, cellular, and molecular levels will be introduced from the perspective of their interplay with HIV and simian immunodeficiency virus (SIV). An emphasis will be placed on studies using SIV/non-human primate (NHP) models that shape current models of HIV pathogenesis. Finally, studies modulating the innate system in vivo in NHPs will be discussed.

High expression of CD161 on CD8+ T cells is associated with a population of cells thought to play a role in mucosal immunity. We wished to investigate this subset in an HIV and Mycobacterium tuberculosis (MTB) endemic African setting.

A flow cytometric approach was used to assess the frequency and phenotype of CD161++CD8+ T cells. 80 individuals were recruited for cross-sectional analysis: controls (n = 13), latent MTB infection (LTBI) only (n = 14), pulmonary tuberculosis (TB) only (n = 9), HIV only (n = 16), HIV and LTBI co-infection (n = 13) and HIV and TB co-infection (n = 15). The impact of acute HIV infection was assessed in 5 individuals recruited within 3 weeks of infection. The frequency of CD161++CD8+ T cells was assessed prior to and during antiretroviral therapy (ART) in 14 HIV-positive patients.

CD161++CD8+ T cells expressed high levels of the HIV co-receptor CCR5, the tissue-homing marker CCR6, and the Mucosal-Associated Invariant T (MAIT) cell TCR Vα7.2. Acute and chronic HIV were associated with lower frequencies of CD161++CD8+ T cells, which did not correlate with CD4 count or HIV viral load. ART was not associated with an increase in CD161++CD8+ T cell frequency. There was a trend towards lower levels of CD161++CD8+ T cells in HIV-negative individuals with active and latent TB. In those co-infected with HIV and TB, CD161++CD8+ T cells were found at low levels similar to those seen in HIV mono-infection.

The frequencies and phenotype of CD161++CD8+ T cells in this South African cohort are comparable to those published in European and US cohorts. Low-levels of this population were associated with acute and chronic HIV infection. Lower levels of the tissue-trophic CD161++ CD8+ T cell population may contribute to weakened mucosal immune defense, making HIV-infected subjects more susceptible to pulmonary and gastrointestinal infections and detrimentally impacting on host defense against TB.

• Adolescent
• Adult
• Anti-HIV Agents/therapeutic use
• CD8-Positive T-Lymphocytes/immunology
• Case-Control Studies
• Cohort Studies
• Cross-Sectional Studies
• Female
• HIV Infections/complications
• HIV Infections/drug therapy
• HIV Infections/immunology
• Humans
• Immunity, Mucosal
• Latent Tuberculosis/complications
• Latent Tuberculosis/immunology
• Lymphocyte Count
• Male
• Middle Aged
• NK Cell Lectin-Like Receptor Subfamily B/metabolism
• South Africa
• T-Lymphocyte Subsets/immunology
• Tuberculosis, Pulmonary/complications
• Tuberculosis, Pulmonary/immunology
• Young Adult

• T32 AI007387 NIAID NIH HHS
• R01 AI097138 NIAID NIH HHS
• AI 007387 NIAID NIH HHS
• 1U19AI082630-01 NIAID NIH HHS
• WT019663MA Wellcome Trust
• AI 097138 NIAID NIH HHS
• 091663 Wellcome Trust
• U19 AI082630 NIAID NIH HHS
• Wellcome Trust
• P30 AI060354 NIAID NIH HHS
• U01 AI095776 NIAID NIH HHS

• FoxP3
• IL-17A
• Morphine
• Th17 cells
• Treg cells
• β7 integrin

• Act1
• IL-17R
• Interleukin 17
• Signaling transduction

• Animals
• Humans
• Inflammation/pathology
• Interleukin-17/metabolism
• Microbiota
• Protein Binding
• Receptors, Interleukin-17/chemistry
• Receptors, Interleukin-17/metabolism
• Signal Transduction

• R01 HL098935 NHLBI NIH HHS
• R01 NS071996 NINDS NIH HHS
• T32 AI089474 NIAID NIH HHS
• U10 HL109250 NHLBI NIH HHS
• P01 HL103453 NHLBI NIH HHS
• T32 GM007250 NIGMS NIH HHS

• candida albicans
• il-17
• th17
• adaptive immunity
• oral mucosal immunity

• Citrobacter rodentium
• FOXP3+CD8+
• IL-17
• MHC class II
• Tc17

• cytotoxic t lymphocytes
• cd8+ t cell
• siv
• hiv
• intestine
• mucosal immunology

• Animals
• Antigens, CD/immunology
• Cell Lineage
• Granzymes/immunology
• Granzymes/metabolism
• Immunity, Mucosal
• Interferon-gamma/immunology
• Interferon-gamma/metabolism
• Interleukin-17/deficiency
• Interleukin-17/genetics
• Interleukin-17/immunology
• Interleukins/deficiency
• Interleukins/genetics
• Interleukins/immunology
• Intestinal Mucosa/immunology
• Intestinal Mucosa/pathology
• Intestinal Mucosa/virology
• Jejunum/immunology
• Jejunum/pathology
• Jejunum/virology
• Killer Cells, Natural/immunology
• Killer Cells, Natural/pathology
• Killer Cells, Natural/virology
• Lymphocyte Count
• Lymphocyte Depletion
• Macaca mulatta
• NK Cell Lectin-Like Receptor Subfamily C/immunology
• NK Cell Lectin-Like Receptor Subfamily K/immunology
• Simian Acquired Immunodeficiency Syndrome/immunology
• Simian Acquired Immunodeficiency Syndrome/pathology
• Simian Acquired Immunodeficiency Syndrome/virology
• Simian Immunodeficiency Virus/physiology
• Th17 Cells/immunology
• Th17 Cells/pathology
• Th17 Cells/virology
• Tumor Necrosis Factor-alpha/immunology
• Tumor Necrosis Factor-alpha/metabolism
• Interleukin-22

• AI49080 NIAID NIH HHS
• P51 RR000164 NCRR NIH HHS
• P51 OD011104 NIH HHS
• R01 AI084793 NIAID NIH HHS
• RR000164 NCRR NIH HHS
• R01 AI049080 NIAID NIH HHS
• AI084793 NIAID NIH HHS

• Animals
• Antigens, CD/immunology
• Cell Differentiation
• Cell Lineage
• Coculture Techniques
• Colon/immunology
• Colon/pathology
• Colon/virology
• Dendritic Cells/immunology
• Dendritic Cells/pathology
• Dendritic Cells/virology
• Enterocytes/immunology
• Enterocytes/pathology
• Enterocytes/virology
• Gene Expression Regulation
• Immunity, Mucosal
• Integrin alpha Chains/deficiency
• Integrin alpha Chains/immunology
• Interleukin-17/deficiency
• Interleukin-17/genetics
• Interleukin-17/immunology
• Interleukins/deficiency
• Interleukins/genetics
• Interleukins/immunology
• Macaca mulatta
• Nuclear Receptor Subfamily 1, Group F, Member 3/genetics
• Nuclear Receptor Subfamily 1, Group F, Member 3/immunology
• Simian Acquired Immunodeficiency Syndrome/immunology
• Simian Acquired Immunodeficiency Syndrome/pathology
• Simian Acquired Immunodeficiency Syndrome/virology
• Simian Immunodeficiency Virus/physiology
• Th17 Cells/immunology
• Th17 Cells/pathology
• Th17 Cells/virology
• Interleukin-22

• Z99 AI999999 Intramural NIH HHS
• HHSN261200800001C NCI NIH HHS
• R01 AI-084836 NIAID NIH HHS
• ZIA AI001029-04 Intramural NIH HHS
• R01 AI084836 NIAID NIH HHS
• HHSN261200800001E NCI NIH HHS