The graft-versus-host reaction (GVHR) induced by inoculating parental T cells into unirradiated F1 hosts is a complex process. Donor repopulation of host lymphohematopoietic tissues requires both CD4+ and CD8+ donor T cells, and the immune dysregulation resulting from such a GVHR appears to involve a switch from a predominance of Thl to Th2 type of helper function. By inducing a GVHR in a parent-F1 combination in which the Mls locus would be recognized, we demonstrated that recognition of Mls determinants contributes to immune suppression in the parent-into-F1 GVHR model, and contributes to mortality in irradiated mice given allogeneic bone marrow differing at Mls. Studies of susceptibility and resistance of mice to infection with Toxoplasma gondii indicated that T. gondii-specific, CD8+ mediated cytolysis is a chronic and acute GVHR, we found that both CD4+ and CD8+ T cell function is important in resistance to this parasite. Studies of the affects of cyclosporin A on murine lymphopoiesis indicates that this immunosuppressive drug: a) selectively abrogates single-positive T cells; b) inhibits the development of TCR-expressing single-positive T cells; and c) augments natural killer cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009259-14
Application #
3796541
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code