CD38 EXPRESSION ON MOUSE T-CELLS - CD38 DEFINES FUNCTIONALLY DISTINCT SUBSETS OF ALPHA-BETA-TCR(+)CD4(-)CD8(-) THYMOCYTES

We have examined CD38 expression on mouse lymphocytes using the rat mAb NIM-R5 and demonstrate that CD38 expression is restricted to similar to 8% of thymocytes. Although CD38 is absent from the majority of CD4(+)CD8(-) and CD4(-)CD8(+) T cells, we detected a strong correlation between CD38 expression and alpha beta(+)CD4(-)CD8(-) T cells in the thymus, with nearly 80% of alpha beta TCR(+)CD4(-)CD8(-)thymocytes being CD38(+). Using heat stable antigen (HSA) and CD38, we divided alpha beta(+)CD4(-)CD8(-)thymocytes into four subsets: HSA(+)CD38(-), HSA(-)CD38(hi), HSA(-)CD38(low) and HSA(-)CD38(-). Two established characteristics of ap TCR(+)CD4(-)CD8(-) cells, bias towards V(beta)8.2 TCR expression and high levels of IL-4 production, were used to establish a possible relationship between the above thymocyte subsets. Our present data show that the HSA(+)CD38(-) subset is not biased towards V(beta)8.2 TCR expression whereas the HSA(-)CD38(-) subset does show this bias (similar to 47%). Neither of these subsets make IL-4 upon CD3 mediated stimulation. In contrast, the CD38(+) subsets are heavily biased toward V(beta)8.2 expression and produce large amounts of IL-4 upon stimulation, particularly the CD38(low) cells. Taken together, these data suggest that these four subsets represent various stages of a possible differentiation pathway for alpha beta TCR(+)CD4(-)CD8(-) cells, with the HSA(+)CD38(-) subset being the most immature while the HSA-CD38(low) subset is the most functionally mature. These characteristics support the view that alpha beta TCR(+)CD4(-)CD8(-) T cells represent an independent lineage with a distinct, but as yet obscure, role in immunity.