IN-VITRO RESPONSES OF HUMAN CD45RO(BRIGHT)RA(-) AND CD45RO(-)RA(BRIGHT) T-CELL SUBSETS AND THEIR RELATIONSHIP TO MEMORY AND NAIVE T-CELLS

The cellular basis of immunological memory, particularly with respect to T cells is not understood. In humans, monoclonal antibodies to CD45 have been used to identify memory (CD45R0) and naive (CD45RA) T cells . However, this identification has been called into question by variou s studies which suggest that high molecular weight CD45 isoforms may b e re-expressed by previously activated cells. In the present study, us ing cultures which supported responses of naive T cells, we examined t he responses of purified CD45R0(high)RA(-) or CD45R0(-)-RA(bright) T c ell subsets. The former subset was found to respond preferentially to recall antigens with minimal responses apparent to neo-(or non-recall) -antigens. The inverse pattern was found for CD45R0(-)RA(bright) T cel ls, which converted to CD45R0(bright)RA(-) after stimulation with a ne o-antigen. Moreover, the two populations of T cells exhibited distinct response kinetics with a faster response evident from the CD45R0(brig ht)RA(-) T cells compared to the CD45R0(-)RA(bright) subset. The poor responses of CD45R0(-)RA(bright) T cells to recall antigens compared t o neo-antigens suggests that this putative naive population is specifi cally depleted of reactive T cells following an encounter with antigen . We propose that T cell priming results in the stimulation of many CD 45R0(-)RA(bright) T cells with various T cell receptor specificities f rom which memory T cells are selected for survival. If re-expression o f higher molecular weight isoforms does occur in humans in vivo, our r esults suggest that R0 expression would be retained (CD45R0(+)RA(+)). Alternatively, if primed CD45R0(-)RA(bright) T cells exist, they are n ot prevalent in peripheral blood and thus may be sequestered within ly mphoid tissues. Our data support the view that in human peripheral bro od, CD45R0(bright) and CD45RA(bright) expression identify memory and n aive CD4(+) T cells, respectively.