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World J Stem Cells. Feb 26, 2017; 9(2): 37-44
Published online Feb 26, 2017. doi: 10.4252/wjsc.v9.i2.37
Impact of T cells on hematopoietic stem and progenitor cell function: Good guys or bad guys?
Sulima Geerman, Martijn A Nolte
Sulima Geerman, Martijn A Nolte, Sanquin Research, Department of Hematopoiesis, Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, 1066CX Amsterdam, The Netherlands
Author contributions: Geerman S and Nolte MA wrote the paper.
Supported by a fellowship obtained by Nolte MA from the Landsteiner Foundation for Blood Transfusion Research (www.lsbr.nl), No. #1014.
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Martijn A Nolte, PhD, Sanquin Research, Department of Hematopoiesis, Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, 1066CX Amsterdam, The Netherlands. m.nolte@sanquin.nl
Telephone: +31-20-5123377 Fax: +31-20-5123474
Received: August 26, 2016
Peer-review started: August 26, 2016
First decision: November 17, 2016
Revised: December 22, 2016
Accepted: January 11, 2017
Article in press: January 14, 2017
Published online: February 26, 2017
Processing time: 182 Days and 3.3 Hours
Abstract

When hematopoietic stem and progenitor cells (HSPC) are harvested for transplantation, either from the bone marrow or from mobilized blood, the graft contains a significant number of T cells. It is these T cells that are the major drivers of graft-vs-host disease (GvHD). The risk for GvHD can simply be reduced by the removal of these T cells from the graft. However, this is not always desirable, as this procedure also decreases the engraftment of the transplanted HSPCs and, if applicable, a graft-vs-tumor effect. This poses an important conundrum in the field: T cells act as a double-edged sword upon allogeneic HSPC transplantation, as they support engraftment of HSPCs and provide anti-tumor activity, but can also cause GvHD. It has recently been suggested that T cells also enhance the engraftment of autologous HSPCs, thus supporting the notion that T cells and HSPCs have an important functional interaction that is highly beneficial, in particular during transplantation. The underlying reason on why and how T cells contribute to HSPC engraftment is still poorly understood. Therefore, we evaluate in this review the studies that have examined the role of T cells during HSPC transplantation and the possible mechanisms involved in their supporting function. Understanding the underlying cellular and molecular mechanisms can provide new insight into improving HSPC engraftment and thus lower the number of HSPCs required during transplantation. Moreover, it could provide new avenues to limit the development of severe GvHD, thus making HSPC transplantations more efficient and ultimately safer.

Keywords: Hematopoietic stem cells; Hematopoietic stem and progenitor cells; CD8 T cells; Transplantation; Engraftment; Memory T cells; Facilitating cells; Bone marrow

Core tip: T cells act as a double-edged sword upon allogeneic hematopoietic stem and progenitor cells (HSPC) transplantation, as they support engraftment of HSPCs and provide anti-tumor activity, but are also the cause of graft-vs-host disease (GvHD). Here, we discuss the findings from several studies that have addressed the still enigmatic role of T cells during HSPC transplantation, either in an allogeneic or autologous setting, in mice or men, and with HSPCs derived from bone marrow, peripheral blood or cord blood. We anticipate that a better comprehension of how T cells support HSPC engraftment may lead to new strategies to optimize HSPCs transplantations and prevent GvHD.