Naturally occurring memory (CD44hi) CD4 T cell responses are differentially regulated by the expression of programmed death-1 receptor (82.4)

Abstract

Abstract CD4 T cells in unprimed mice can acquire CD44hi memory phenotype (MP) and the MP CD4 T cell subset become progressively more prominent with age. Although it is not clearly evident if MP CD4 T cells arise due to lymphopenia-induced proliferation or environmental antigen exposure, studies carried out in mice model suggest that naturally occurring MP CD4 T cells are hyporesponsive to both polyclonal and TCR mediated stimulus. In this report we determined that a large proportion of naturally occurring MP CD4 T cell pool in unprimed mice expressed multiple inhibitory receptor PD-1, ICOS and CTLA-4. Furthermore, inhibitory receptor expressing MP CD4 T cells become more prominent with advancing age. Our results showed that PD-1hi MP CD4 T cells isolated from aged mice were more susceptible to spontaneous apoptosis when compared with PD-1lo MP CD4 T cells. We also determined the differential expression of IFN-γ, IL-2 and IL-17 cytokines in PD-1+ versus PD-1- MP CD4 T cells isolated from unprimed young and old mice. Lastly, MP CD4 T cells purified from aged mice proliferated differentially to Con A stimulus depending on the expression of PD-1 receptor. Thus, we conclude that responses of naturally occurring MP CD4 T cells are differentially regulated by the expression of inhibitory PD-1 receptor. Supported by the funds derived from American Federation for Aging Research (AFAR).