REDUCED THYMIC MATURATION BUT NORMAL EFFECTOR FUNCTION OF CD8-CELLS IN CD8-BETA GENE-TARGETED MICE( T)

CD8 is a cell surface glycoprotein on major histocompatibility complex class I-restricted T cells. Thymocytes and most peripheral T cells ex press CD8 as heterodimers of CD8 alpha and CD8 beta. The intestinal in traepithelial lymphocytes (IEL), which have been suggested to be gener ated extrathymically, express CD8 predominantly as homodimers of CD8 a lpha. We have generated CD8 beta gene-targeted mice. CD8 alpha(+) T ce ll population in the thymus and in most peripheral lymphoid organs was reduced to 20-30% of that in wild-type littermates. CD8 alpha express ion on thymocytes and peripheral T cells also decreased to 44 and 53% of the normal levels, respectively. In contrast, neither the populatio n size nor the CD8 alpha expression level of CD8 alpha(+) IEL was redu ced. This finding indicates that CD8 beta is important only for thymic -derived CD8(+) T cells. The lack of CD8 beta reduces but does not com pletely abolish thymic maturation of CD8(+) T cells. Our result also r eveals the role of CD8 beta in regulating CD8 alpha expression on thym ic derived T cells. Peripheral T cells in these mice were efficient in cytotoxic activity against lymphocytic choriomeningitis virus and ves icular stomatitis virus, suggesting that CD8 beta is not essential for the effector function of CD8(+) T cells.