Differential kinetics of antigen-specific CD4+ and CD8+ T cell responses in the regression of retrovirus-induced sarcomas

Despite the accepted role for CD4(+) T cells in immune control, little is known about the development of Ag-specific CD4(+) T cell immunity upon primary infection. Here we use MHC class H tetramer technology to directly visualize the Ag-specific CD4(+) T cell response upon infection of mice with Moloney murine sarcoma and leukemia virus complex (MoMSV). Significant numbers of Ag-specific CD4(+) T cells are detected both in lymphoid organs and in retrovirus-induced lesions early during infection, and they express the 1B11-reactive activation-induced isoform of CD43 that was recently shown to define effector CD8(+) T cell populations. Comparison of the kinetics of the MoMSV-specific CD4(+) and CD8(+) T cell responses reveals a pronounced shift toward CD8(+) T cell immunity at the site of MoMSV infection during progression of the immune response. Consistent with an important early role of Ag-specific CD4(+) T cell immunity during MoMSV infection, CD4+ T cells contribute to the generation of virus-specific CD8(+) T cell immunity within the lymphoid organs and are required to promote an inflammatory environment within the virus-infected tissue.