title: The role of CD28 costimulation in immune-mediated responses against mouse mammary tumor viruses.
abstract: 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.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Palmer
authors.forename: B
authors.initials: B
authors.lastname: Saha
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodes
authors.forename: R
authors.initials: R
authors.lastname: Abe
mesh_terms: 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
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta