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Memory Phenotype of CD8⁺ T Cells in MHC Class Ia-Deficient Mice¹

^* Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390

B6.K^b-D^b- 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 CD8 T cells is increased in these animals, 90% of CD8 T cells are CD8. In contrast to B6 animals, most of the CD8 T cells from these mice have a memory phenotype (CD44^highCD122^high CD62L^low) including both CD8 and CD8 subsets. In the thymus of B6.K^b-D^b- animals, there is a decrease in the percentage of SP CD8 T cells, although most are CD44^low, similar to that seen in B6 mice. The spleens from day 1-old B6 and B6.K^b-D^b- mice have a relatively high proportion of CD44^highCD62L^low CD8 T cells. However, by day 28 most CD8 T cells in B6 mice have a naive phenotype while in B6.K^b-D^b- mice the memory phenotype remains. Unlike CD44^high cells that are found in B6 animals, most CD44^high cells from B6.K^b-D^b- mice do not secrete IFN- rapidly upon activation. The paucity of CD8 T cells in B6.K^b-D^b- 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.

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