CD45RB EXPRESSION DEFINES 2 INTERCONVERTIBLE SUBSETS OF HUMAN CD4(+) T-CELLS WITH MEMORY FUNCTION

Reciprocal expression of CD45RA and CD45RO in human CD4(+) T cells defines populations understood to be naive cells (CD45RA(+)CD45RO(-)) and memory cells (CD45RA(-)CD45RO(+)). We investigate two subsets of CD45RA(-)CD45RO(+) CD4(+) human T cells which differ by fourfold in their expression of the CD45RB isoform; one is CD45RB(bright) and the other is CD45RB(intermediate). In contrast, CD45RA(+) naive cells are all CD45RB(bright). Both subsets of CD45RA(-) cells proliferate in response to recall antigens so we designate them MEM 1 (CD45RO(+)RB(bright)) and MEM 2 (CD45RO(+)RB(intermediate)). CD45RA and CD45RB expression are regulated independently during bt vitro activation of naive cells. When MEM 1 cells are activated they tend to down-regulate CD45RB expression, whereas activated MEM 2 cells tend to up-regulate CD45RB expression. Thus, in contrast to the stability of the CD45RA(-)CD45RO(+) phenotype, the MEM 1 and MEM 2 phenotypes are labile and may interconvert. MEM 1 and MEM 2 cells produced comparable amounts of interleukin(IL)-2, IL-4, and IL-5 though MEM 1 cells produced slightly more interferon(IFN)-gamma (mean 1.7-fold more). MEM 1 cells consistently proliferated more (mean 2.3-fold more) than MEM 2 cells early during in vitro activation. Thus, differential expression of CD45RB within CD45RA(-) cells defines two subsets that have similar properties except for somewhast greater IFN-gamma production and proliferative responses by MEM 1 cells. Variability in CD45RB expression may represent a mechanism for fine-tuning the responsiveness of memory cells in vivo.