Functional and ontogenetic analysis of murine CD45R(hi) and CD45R(lo) CD4⁺ T cells

CD4⁺ murine T cell clones, T(H1) and T(H2), can be distinguished by both functional responses and by their patterns of lymphokine secretion. Recently, a mAb, 23G2, which reacts with a subset of CD45 molecules (CD45R), has been reported to bind differentially to clones of T(H1) and T(H2) cells. In the present study, normal splenic T cells were analyzed for differences in 23G2-reactivity and were separated into two populations based on their density of CD45R (CD45R(hi) and CD45R(lo)). The CD45R(hi) cells secrete more IL-2 than IL-4 after stimulation in vitro; the reverse is true for the CD45R(lo) cells. Because neither population secretes only IL-2 or IL-4, we were unable to classify cells as T(H1) or T(H2). In vivo and in vitro analyses of the CD45R(hi) and CD45R(lo) cells suggest a lineage relationship between the two subsets that correlates with the degree of Ag exposure and the state of maturation of the mice. In newborn mice and mice raised under sterile conditions, splenic CD4⁺ T cells are predominantly CD45R(hi). Under conditions of increased antigenic exposure and maturation of the mice, CD45R(lo) cells develop; after long term priming in vivo, the majority of specific Ag-reactive cells are CD45R(lo). Adoptive transfer studies using BALB/c nu/nu recipients demonstrate that CD45R(hi) cells become CD45R(lo) cells and that the recall response (IgG) to specific Ag is mediated by CD45R(lo) cells. Taken together, these data indicate that the level of expression of CD45R on CD4⁺ T cells distinguishes virgin (CD45R(hi)) from primed/memory (CD45R(lo)) T cells in normal mice.