THE ROLE OF CD28 COSTIMULATION IN IMMUNE-MEDIATED RESPONSES AGAINST MOUSE MAMMARY-TUMOR VIRUSES

Infectious mouse mammary tumor viruses (MMTV) encode superantigens (SA g) which, when presented in association with permissive class II MHC m olecules, are recognized by those T cells that express appropriate TCR s. Recent findings have indicated that expression of a permissive MHC class II product and of a specific TCR are also critical to susceptibi lity of newborn mice to infection with milk-borne MMTV, suggesting tha t SAg-mediated T cell activation may play a facilitating role in viral infection. Because effective Ag-specific T cell activation can requir e costimulatory signals in addition to TCR-mediated recognition, the r ole of the CD28 costimulatory receptor was analyzed in responses of ne onatal and adult mice to MMTV challenge. Mice that were deficient in C D28 expression as a result of gene targeting were compared with CD28-i ntact 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 optim al T and B cell responses to MMTV challenge, as reflected in the param eters measured, are CD28 dependent, In contrast, CD28 absence did not impair TCR-V beta-specific clonal deletion induced by neonatal exposur e to MMTV, Further, analysis of susceptibility to viral infection in n eonatally exposed mice revealed that CD28 deficiency did not interfere with SAg-dependent MMTV infection, Failure to identify CD28 dependenc e of MMTV infection suggests either the absence of a costimulatory req uirement in the events that lead to viral infection or a redundancy in costimulatory signals that support infection.