Reduced thymic maturation but normal effector function of CD8+ T cells in CD8β gene-targeted mice

Abstract

CD8 is a cell surface glycoprotein on major histocompatibility complex class I-restricted T cells. Thymocytes and most peripheral T cells express CD8 as heterodimers of CD8α and CD8β. The intestinal intraepithelial lymphocytes (IEL), which have been suggested to be generated extrathymically, express CD8 predominantly as homodimers of CD8α. We have generated CD8β gene-targeted mice. CD8α+ T cell population in the thymus and in most peripheral lymphoid organs was reduced to 20-30% of that in wild-type littermates. CD8α expression on thymocytes and peripheral T cells also decreased to 44 and 53% of the normal levels, respectively. In contrast, neither the population size nor the CD8α expression level of CD8α+ IEL was reduced. This finding indicates that CD8β is important only for thymic- derived CD8+ T cells. The lack of CD8β reduces but does not completely abolish thymic maturation of CD8+ T cells. Our result also reveals the role of CD8β in regulating CD8α expression on thymic derived T cells. Peripheral T cells in these mice were efficient in cytotoxic activity against lymphocytic choriomeningitis virus and vesicular stomatitis virus, suggesting that CD8β is not essential for the effector function of CD8+ T cells.