Infectious mouse mammary tumor viruses (MMTV) encode superantigens (SAg) which, when presented in association with permissive class II MHC molecules, are recognized by those T cells that express appropriate TCRs. Recent findings have indicated that expression of a permissive MHC class II product and of a specific TCR are also critical to susceptibility of newborn mice to infection with milk-borne MMTV, suggesting that SAg-mediated T cell activation may play a facilitating role in viral infection. Because effective Ag-specific T cell activation can require costimulatory signals in addition to TCR-mediated recognition, the role of the CD28 costimulatory receptor was analyzed in responses of neonatal and adult mice to MMTV challenge. Mice that were deficient in CD28 expression as a result of gene targeting were compared with CD28-intact littermates. In response to parenteral challenge with MMTV, CD28-deficient adult mice exhibited reduced expansion of MMTV SAg-reactive T cells in draining LNs, decreased cytokine production, and decreased B cell activation and Ig secretion. These results indicate that optimal T and B cell responses to MMTV challenge, as reflected in the parameters measured, are CD28 dependent. In contrast, CD28 absence did not impair TCR-V beta-specific clonal deletion induced by neonatal exposure to MMTV. Further, analysis of susceptibility to viral infection in neonatally exposed mice revealed that CD28 deficiency did not interfere with SAg-dependent MMTV infection. Failure to identify CD28 dependence of MMTV infection suggests either the absence of a costimulatory requirement in the events that lead to viral infection or a redundancy in costimulatory signals that support infection.

This content is only available via PDF.
You do not currently have access to this content.