CD28/CTLA-4/B7 and CD40/CD40L costimulation and activation of regulatory T cells

Figure 2 The potential effects of a cytotoxic T lymphocyte-associated antigen-4Ig treatment started before T cell priming. If cytotoxic T lymphocyte antigen (CTLA)-4Ig is given before T cell priming at a low dose, it reduces CD28 mediated T cell activation. Since blockade of B7 molecules is not complete, some Teff cells are still activated and produce interleukin (IL)-2. Treg cell-activation is less or not dependent on CD28 signalling and the low amounts of IL-2 produced by the Teff cells are sufficient to maintain Treg cell activation. In that way activated Treg cells further suppress the remaining Teff cells. The effect of CTLA-4Ig is in this situation based on down-regulation of Teff cells and maintenance of Treg activity (A). If CTLA-4Ig is given at a high concentration, Teff and Treg cells are equally suppressed due to missing costimulation and/or IL-2. The effect of CTLA-4Ig is in this case based on reduced Teff cell activity (B). APC: Antigen presenting cell, Teff: effector T cell, Treg: Regulatory T cell.