Exogenous retroviruses were analyzed for their influences on T cell repertoire. A defective murine leukemia virus which causes a mouse acquired immune deficiency syndrome (MAIDS) induced superantigen-like T cell activation in vitro. In vivo, this virus selectively activated and expanded CD4+ T cells expressing Vß5, followed later in the course of infection by widespread immune deficiency in all T cells.The effect of milk-borne MMTV on the T cell receptor (TCR) repertoire was analyzed. A previously uncharacterized tumorigenic milk-borne virus in BALB/c mice (the BALB/cV virus) was found to induce deletion of T cells expressing TCR Vß2 in developing mice. The roles of MHC class II, TCR, and CD28 costimulatory molecules in susceptibility to MMTV infection were tested. Milk-borne virus induced Vß-specific deletion only in strains of mice bearing natural or transgenic I-E class II major histocompatibility complex (MHC) product. Moreover, susceptibility to milk-borne virus as determined by assays of viral pp28 or LTR mRNA was also dependent upon I-E expression. These findings indicate that viral infection is dependent upon superantigenic stimulation of host lymphoid cells. Studies employing CD28-deficient mice indicated that CD28-dependent costimulus plays a role in Vß- specific T and B cell responses to in vivo challenge of adult mice with infectious MMTV. In contrast, Vß-specific deletion in response to neonatal challenge, as well as susceptibility to infectious milk-borne virus, appeared to be CD28-independent.The role of costimulation is being studied in T cell repertoire selection. Mice that are either over-expressing or deficient in costimulatory molecules B7-1 and B7-2 or the costimulatory receptor CD28 are being analyzed for expressed T cell repertoire. Endogenous proviral antigens as well as the effect of fetal-specific antigens in a T cell receptor transgenic model of pregnancy are being analyzed. - anitigen presentation, immune response, immunology, lymphocytes, receptors, T lymphocytes,
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| Vacchio, Melanie S; Hodes, Richard J (2005) Fetal expression of Fas ligand is necessary and sufficient for induction of CD8 T cell tolerance to the fetal antigen H-Y during pregnancy. J Immunol 174:4657-61 |
| Vacchio, Melanie S; Williams, Joy A; Hodes, Richard J (2005) A novel role for CD28 in thymic selection: elimination of CD28/B7 interactions increases positive selection. Eur J Immunol 35:418-27 |
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| Vacchio, Melanie S; Hodes, Richard J (2003) CD28 costimulation is required for in vivo induction of peripheral tolerance in CD8 T cells. J Exp Med 197:19-26 |
