Memory Phenotype of CD8+ T Cells in MHC Class Ia-Deficient Mice

B6.Kb−Db− mice are devoid of class Ia but express normal levels of class Ib molecules. They have low levels of CD8 T cells in both the thymus as well as peripheral T cell compartments. Although the percentage of splenic CD8αα T cells is increased in these animals, ∼90% of CD8 T cells are CD8αβ. In contrast to B6 animals, most of the CD8 T cells from these mice have a memory phenotype (CD44highCD122high CD62Llow) including both CD8αβ and CD8αα subsets. In the thymus of B6.Kb−Db− animals, there is a decrease in the percentage of SP CD8 T cells, although most are CD44low, similar to that seen in B6 mice. The spleens from day 1-old B6 and B6.Kb−Db− mice have a relatively high proportion of CD44highCD62Llow CD8 T cells. However, by day 28 most CD8 T cells in B6 mice have a naive phenotype while in B6.Kb−Db− mice the memory phenotype remains. Unlike CD44high cells that are found in B6 animals, most CD44high cells from B6.Kb−Db− mice do not secrete IFN-γ rapidly upon activation. The paucity of CD8 T cells in B6.Kb−Db− mice might be due in part to their inability to undergo homeostatic expansion. Consistent with this, we found that CD8 T cells from these animals expand poorly in X-irradiated syngeneic hosts compared with B6 CD8 T cells that respond to class Ia Ags. We examined homeostatic expansion of B6 CD8 T cells in single as well as double class Ia knockout mice and were able to estimate the fraction of cells reactive against class Ia vs class Ib molecules.