CD38 expression on mouse T cells: CD38 defines functionally distinct subsets of alpha beta TCR super(+)CD4 super(-)CD8 super(-) 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 super(+)CD8 super(-) and CD4 super(-)CD8 super(+) T cells, we detected a strong correlation between CD38 expression and alpha beta super(+)CD4 super(-)CD8 super(-) T cells in the thymus, with nearly 80% of alpha beta TCR super(+)CD4 super(-)CD8 super(-) thymocytes being CD38 super(+). Using heat stable antigen (HSA) and CD38, we divided alpha beta super(+)CD4 super(-)CD8 super(-) thymocytes into four subsets: HSA super(+)CD38 super(-), HSA super(-)CD38 super(hi), HSA super(-)CD38 super(low) and HSA super(-)CD38 super(-). Two established characteristics of alpha beta TCR super(+)CD4 super(-)CD8 super(-) cells, bias towards V sub( 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 super(+)CD38 super(-) subset is not biased towards V sub( beta )8.2 TCR expression whereas the HSA super(-)CD38 super(-) subset does show this bias ( similar to 47%). Neither of these subsets make IL-4 upon CD3 mediated stimulation. In contrast, the CD38 super(+) subsets are heavily biased toward V sub( beta )8.2 expression and produce large amounts of IL-4 upon stimulation, particularly the CD38 super(low) cells. Taken together, these data suggest that these four subsets represent various stages of a possible differentiation pathway for alpha beta TCR super(+)CD4 super(-)CD8 super(-) cells, with the HSA super(+)CD38 super(-) subset being the most immature while the HSA super(-)CD38 super(low) subset is the most functionally mature. These characteristics support the view that alpha beta TCR super(+)CD4 super(-)CD8 super(-) T cells represent an independent lineage with a distinct, but as yet obscure, role in immunity.