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Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
Classical CD4+ and CD8+ T cells recognize Ag presented by MHC class II (MHCII) and MHC class I (MHCI), respectively. However, our results show that CD4–/– mice mount a strong, readily detectable CD8+ T cell response to MHCII-restricted epitopes after a primary bacterial or viral infection. These MHCII-restricted CD8+CD4– T cells are more similar to classical CD8+ T cells than to CD4+ T cells in their expression of effector functions during a primary infection, yet they also differ from MHCI-restricted CD8+ T cells by their inability to produce high levels of the cytolytic molecule granzyme B. After resolution of a primary infection, epitope-specific MHCII-restricted T cells in CD4–/– mice persist for a long period of time as memory T cells. Surprisingly, upon reinfection the secondary MHCII-restricted response in CD4–/– mice consists mainly of CD8–CD4– T cells. In contrast to CD8+ T cells, MHCII-restricted CD8–CD4– T cells are capable of producing IL-2 in addition to IFN-
and thus appear to have attributes characteristic of CD4+ T cells rather than CD8+ T cells. Therefore, MHCII-restricted T cells in CD4–/– mice do not share all phenotypic and functional characteristics with MHCI-restricted CD8+ T cells or with MHCII-restricted CD4+ T cells, but, rather, adopt attributes from each of these subsets. These results have implications for understanding thymic T cell selection and for elucidating the mechanisms regulating the peripheral immune response and memory differentiation.
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