CD8⁺CD28⁻ T suppressor cells and the induction of antigen‐specific, antigen‐presenting cell‐mediated suppression of Th reactivity

Abstract

Human CD8+CD28- suppressor T cells (Ts) are a subset of T cells generated in the course of in vitro and in vivo immunizations. Ts recognize MHC class I:peptide complexes and inhibit the reactivity of T helper cells (Th) with cognate antigen specificity. We have demonstrated for the first time that CD8+CD28- Ts represent a unique subset of regulatory cells that induces the differentiation of tolerogenic antigen-presenting cells, initiating a suppressive loop which results in the induction and spreading of Th unresponsiveness.

A peptide based on the complementarity-determining region 1 of an autoantibody ameliorates lupus by up-regulating CD4+CD25+cells and TGF-β

“…We therefore suggest that hCDR1-induced CD4 ϩ CD25 ϩ cells cause the ''silencing'' of CD4 ϩ cells as indicated by reduced expression of FasL, consequently with a reduced rate of activation-induced apoptosis (26), rather than causing the depletion of the latter by means of apoptosis. Taken together, our results indicate a key role for CD4 ϩ CD25 ϩ cells in the mechanism of action of hCDR1, although other cell types and mechanisms (36,37) may be involved as well. Based on the present report, we suggest that inhibition by the hCDR1-induced CD4 ϩ CD25 ϩ cells is mediated through TGF-␤, which is secreted by other T cells that are affected by the immunoregulatory cells.…”

CD8 T Cells Modulate CD4 T-Cell and Eosinophil-Mediated Pulmonary Pathology in Pneumocystis Pneumonia in B-Cell-Deficient Mice

“…31 Observations such as these have lead to a resurgence in the study of putative CD8-positive regulatory or suppressor cells. [32][33][34] A major focus in these studies has been CD28 Ϫ CD8 ϩ cells, which are believed to induce tolerance in transplantation models via contact-dependent mechanisms involving antigen-presenting cells and subsequently T helper CD4 cells. 33,35 Whether or not CD8 suppressor cells are involved in this modulation, it is clear that when CD8 T cells are absent in Pneumocystis-infected MT mice, a relative deficit of CD25 ϩ CD4 ϩ T cells occurs.…”

Cellular senescence impact on immune cell fate and function

“…CD28 null T cells are apoptosis resistant, terminally differentiated effectors with eroded telomeres. This population is, however, very heterogeneous and encompasses both effector, senescent and T‐regulatory (Treg) cells (Freedman et al ., 1991; Cortesini et al ., 2001; Chang et al ., 2002; Suciu‐Foca & Cortesini, 2007). …”