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Thymus-Dependent Memory Phenotype CD8 T Cells in Naive B6.H-2K^b–/–D^b–/– Animals Mediate an Antigen-Specific Response against Listeria monocytogenes¹

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

B6.H-2K^b–/–D^b–/– (DKO) mice have greatly reduced numbers of mature CD8 T cells in their periphery. However, these non-class Ia-selected CD8 T cells are able to mediate immune responses to a number of pathogens. Approximately 60% of the CD8 T cells in the spleen and peripheral lymph nodes of naive DKO mice display a memory (CD44^high) phenotype. To investigate the origins of these non-class Ia-selected CD8CD44^high cells, we traced the phenotype of recent thymic emigrants and found that most were CD44^low. We also determined whether their appearance was thymus dependent and found that only a small percentage of non-class Ia-selected CD8CD44^high cells develop in a thymus-independent pathway. Functionally, CD8CD44^high cells from DKO mice are able to secrete IFN- in response to IL-12 and IL-18 in the absence of cognate Ag. When challenged with anti-CD3 in vivo, nearly half of these cells produce IFN- within 3 h. When purified CD8CD44^high cells from Thy1.2.DKO mice were transferred into Thy1.1 DKO recipients and then challenged with Listeria monocytogenes, an Ag-specific anti-L. monocytogenes response was observed 6 days later. Our data suggest that non-class Ia-selected CD8CD44^high cells in naive animals can respond rapidly to Ag and play a role in the innate as well as the early phase of the acquired immune response.

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