Origin and Function of CD8 T Cells in MHC Class Ia-Deficient Mice

B6.H-2Kb-/-Db-/- (DKO) 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, approximately 90% of CD8 T cells are CD8αβTCRαβ. In contrast to B6 animals, most of the CD8 T cells from these mice have a memory phenotype (CD44hi) including both CD8αβ and CD8αα subsets. In the thymus of DKO animals, there is a decrease in the percentage of single positive CD8 T cells, although most are CD44low, similar to that seen in B6 mice. Our results indicated that the paucity of CD8 T cells in DKO mice might be in part due in reduced thymic export, lower basal proliferation, high apoptosis, and inability to undergo homeostatic expansion. DKO mice have greatly reduced numbers of mature CD8αβ T cells in their periphery. However, these non class Ia selected CD8αβ cells are able to mediate immune responses to a number of pathogens. Approximately 60% of the CD8αβ T cells in the spleen and peripheral lymph nodes of naïve DKO mice display a memory (CD44hi) phenotype. To investigate the origins of these non class Ia selected CD8αβCD44hi cells, we traced the phenotype of recent thymic emigrants (RTEs) and found that most were CD44lo. We also determined if their appearance was thymusdependent and found that only a small percentage of non class Ia selected CD8αβCD44hi cells develop in a thymus-independent pathway. Functionally, CD8αβCD44hi cells from DKO mice are able to secrete IFN-γ in response to interleukin (IL)-12 and IL-18 in the absence of cognate antigen. When challenged with anti-CD3 in vivo, nearly half of these cells produce IFN-γ within 3 hours. When purified CD8αβCD44hi cells from Thy1.2.DKO mice were transferred into Thy1.1 DKO recipients and then challenged with Listeria monocytogenes (LM), an antigen specific anti-LM response was observed six days later. Our data suggest that non class Ia selected CD8αβCD44hi cells in naïve animals can respond to antigen and play a role in the innate as well as the early phase of the acquired immune response.