MHC-Independent Thymic Selection of CD4 and CD8 Coreceptor Negative αβ T Cells.

It is becoming increasingly clear that unconventional T cell subsets, such as NKT, gd T, mucosal-associated invariant T, and CD8aa T cells, each play distinct roles in the immune response. Subsets of these cell types can lack both CD4 and CD8 coreceptor expression. Beyond these known subsets, we identify CD42CD82TCRab+, double-negative (DN) T cells, in mouse secondary lymphoid organs. DN T cells are a unique unconventional thymic-derived T cell subset. In contrast to CD5high DN thymocytes that preferentially yield TCRab+ CD8aa intestinal lymphocytes, we find that mature CD5low DN thymocytes are precursors to peripheral DN T cells. Using reporter mouse strains, we show that DN T cells transit through the immature CD4+CD8+ (doublepositive) thymocyte stage. Moreover, we provide evidence that DN T cells can differentiate in MHC-deficient mice. Our study demonstrates that MHC-independent thymic selection can yield DN T cells that are distinct from NKT, gd T, mucosal-associated invariant T, and CD8aa T cells. [ABSTRACT FROM AUTHOR]