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 Va5, 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 Va2 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 Va-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 Va-specific T and B cell responses to in vivo challenge of adult mice with infectious MMTV. In contrast, Va-specific deletion in response to neonatal challenge, as well as susceptibility to infectious milk-borne virus, appeared to be CD28- independent.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC009265-16
Application #
6100956
Study Section
Special Emphasis Panel (EIB)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Williams, Joy A; Lumsden, Joanne M; Yu, Xiang et al. (2008) Regulation of thymic NKT cell development by the B7-CD28 costimulatory pathway. J Immunol 181:907-17
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
Lumsden, Joanne M; Williams, Joy A; Hodes, Richard J (2003) Differential requirements for expression of CD80/86 and CD40 on B cells for T-dependent antibody responses in vivo. J Immunol 170:781-7
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