The role of CD28 costimulation in immune-mediated responses against mouse mammary tumor viruses.
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.
Palmer
L D
LD
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Saha
B
B
Hodes
R J
RJ
Abe
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D007111:Immunity, Cellular / Q000235:genetics; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D008212:Lymphocyte Depletion; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology
D018106:CD28 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta