This proposal focuses on three aspects of the interaction between T lymphocytes and MHC gene products: (i) the cellular basis of specifically induced resistance to GVH disease, (ii) the cellular mechanisms underlying the induction and onset of autoimmune disease in rats undergoing a prolonged course of treatment with cyclosporine A, and (iii) whether common mechanisms based on idiotype-anti-idiotype interactions involving MHC specific T cells and receptor specific regulator T cells underly these two disease models. Previous studies supported by this grant have shown that alloreactive parental strain (A) T cells carry associated marker which behaves like a highly conserved idiotype of anti-MHCb receptors. As an immunogen in adult A/B F1 rats it induces a prolonged and specific T cell mediated state of resistance to GVH disease caused by anti-MHCb T cells from any source. As a tolerogen in newborn A/B F rats it induces an exquisite and specific sensitivity to GVH disease caused by anti-b T cells. The responding F1 T cells include a subset which suppresses alloreactivity-in vivo and is lytic for MLC blasts in vitro. In both cases these """"""""regulator anti-idiotypic T cells do not appear to be MHC restricted. The studies to be performed are designed to explore the possibility that autoreactive T cells (e.g. B anti-b) have the same idiotypic marker found on alloreactive (A anti-b) T cells, and that regulatory, anti-idiotypic T cells control the expression of these idiotypic anti-MHC T cells as part of the ongoing process involved in the maintenance of self tolerance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
7R37AI022519-09
Application #
3481189
Study Section
Immunobiology Study Section (IMB)
Project Start
1990-06-01
Project End
1992-12-31
Budget Start
1992-01-01
Budget End
1992-12-31
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Sidney Kimmel Cancer Center
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92121