Selective immune stimulation during induction of allograft tolerance in the rat by radical immunosuppression.
Recent investigation of a biologically active synthetic polymer, NED 137, has demonstrated its ability to induce a B cell differentiation response to certain antigens, even in the presence of T cell depletion. In this report, the effect of T cell depletion combined with NED 137, on skin allografting, is explored in the Lewis strain rat. Animals were T cell-depleted by thymectomy, total body irradiation, and syngeneic marrow repopulation. They were then challenged with skin allografts +/- NED 137 treatment. Graft survival was significantly prolonged in the T-depleted rats regardless of treatment with NED 137. The drug did not increase the immune response to donor antigen as measured by in vivo lysis of 51Cr-labeled cells. Immunization with heterologous erythrocytes produced a low level of differentiation of IgM-producing cells in the T cell-depleted skin allografted group, but in contrast the T-depleted NED 137-treated rats had a normal response to immunization. These data suggest that selective stimulation of the humoral component of the immune response is feasible at a time when T cell-mediated function has been radically suppressed, without producing adverse effects on allograft survival.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D007165:Immunosuppression Therapy; D008212:Lymphocyte Depletion; D008297:Male; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D011915:Rats, Inbred BUF / Q000276:immunology; D011917:Rats, Inbred Lew / Q000276:immunology; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D011108:Polymers; C022084:carboxyimamidate