The conundrum of immune response: two Ia loci specifically control multiple immune responses.
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Biomedical subjects
C G Fathman
Publications and source records attributed to C G Fathman.
Intrathymic presentation of circulating non-major histocompatibility complex antigens.
Intrathymic selection of T-cell specificity has been shown to be influenced by self-major histocompatibility complex (MHC) antigens encoded by radioresistant thymic stromal cells. The role of non-MHC antigens in intrathymic T-cell differentiation, in particular induction of antigen-specific tolerance, has been unclear and the access of non-MHC antigens to the thymus is controversial. Here we present evidence that circulating protein antigens enter the thymus and are presented by thymic stromal cells. At least three distinct types of stromal cells are thought to be associated with intrathymic lymphopoiesis; after intravenous (i.v.) injection of antigen only I-A/E-positive medullary dendritic cells, but not I-A/E-negative macrophages or I-A/E-positive cortical epithelial cells co-purified with antigen-specific stimulation of cloned T-helper cells in vitro. Antigen presentation by thymic stromal cells was dependent on the dose of antigen injected and the time interval after injection.
Animals↗
Selective T-cell depletion with Ox-38 anti-CD4 monoclonal antibody prevents cardiac allograft rejection in rats.
New monoclonal antibodies directed to membrane molecules unique to lymphocyte subsets have provided the means to alter the immune response to alloantigens in a more selective fashion. This investigation demonstrates that monoclonal antibody-induced depletion of CD4 helper/inducer T lymphocytes before transplantation of a fully mismatched heart allograft allows permanent engraftment in rats without further immunosuppression. Five adult male ACI (RT1a) rats received cell-depleting doses of the mouse anti-rat CD4 monoclonal antibody, MRC Ox-38, for 1 month before undergoing heterotopic abdominal heart transplantation. No other immunosuppression was administered, and immunotherapy was discontinued the day of transplantation. After all five Lewis rat (RT1(1)) hearts were maintained free of rejection for more than 3 months, a second heterotopic transplant was performed, this time to the femoral vessels, using either fresh Lewis heart allografts (n = 3) or third-party, Brown-Norway (RT1n) hearts (n = 2). Histologic evaluation was performed 3 weeks later and revealed severe rejection of the femoral Brown-Norway grafts with no evidence of rejection in any of the femoral or original abdominal Lewis grafts. These results suggested that limited, pretransplant anti-CD4 immunotherapy allowed permanent engraftment of fully mismatched cardiac allografts in rats and conferred donor-specific unresponsiveness.
Abdomen↗