CD8 is needed for positive selection but differentially required for negative selection of T cells during thymic ontogeny

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Abstract
During thymic development, immature thymocytes expressing major histocompatibility complex (MHC) class I‐restricted T cell receptors (TcR) differentiate into CD8+ T cells with cytolytic functions. To evaluate the role of CD8 in positive and negative selection during thymic ontogeny, mice rendered CD8‐null by gene targeting were bred with three lines of transgenic mice expressing unique MHC class I‐restricted TcR. In all three instances CD8 was required for positive selection of MHC class I‐restricted transgenic T cells. The efficiency of positive selection decreased in accordance with a reduced level of CD8 expression on thymocytes. Surprisingly, there was a differential requirement for CD8 expression in negative selection of MHC class I‐restricted thymocytes, depending on the antigen specificity of TcR. These observations show that CD8 is essential for positive selection but is differentially required for negative selection of MHC class I‐restricted T cells. Thus thymic selection, at least for negative selection, can occur in the absence of the CD8 accessory molecule.