OX40-deficient mice are defective in Th cell proliferation but are competent in generating B cell and CTL responses after virus infection

OX40, a member of the TNF receptor superfamily, is expressed on activated T cells and implicated in stimulation of T cells and T-dependent humoral responses. We generated OX40(-/-) mice and found that the formation of extrafollicular plasma cells, germinal centers, and antibody responses was independent of OX40. After infection with LCMV and influenza virus, OX40(-/-) mice retain primary and memory cytotoxic T cell responses with normal expansion and decline of specific CTL. In contrast, CD4(+) T cell proliferation and the number of IFN-gamma-producing CD4(+) T cells were reduced in OX40(-/-) mice. Moreover, the number of CD4(+) T cells infiltrating the lungs of influenza virus-infected OX40(-/-) mice was reduced. These results define a unique role of OX40 in the generation of optimal CD4(+) T cell responses in vivo.