Regulation of the immune response in experimental models of autoimmune disorders: I. Immunocompetence and transplantation tolerance in female (NZB X NZW)F1 hybrid mice immunosuppressed with total lymphoid irradiation and in reconstituted bone marrow chimeras.

Female (NZB X NZW)F1 (B/WF1) mice treated with fractionated total lymphoid irradiation (TLI) and TLI conditioned BALB/c leads to B/WF1 bone marrow (BM) chimeras were studied to determine the effects of TLI and reconstitution with normal BM on in vivo and in vitro immune reactivity. TLI treated B/WF1 females showed limited increased retention of semiallogeneic skin grafts (2 1/2 times as long as untreated) and allogeneic skin grafts (twice as long as untreated). In vitro proliferative responses to allogeneic lymphocytes were severely depressed at 5 days after TLI with partial recovery as early as 15 days post TLI. Proliferative responses to phytohemmagglutinin, concanavalin A and lipopolysaccharide were similarly depressed in the immediate post TLI period with gradual subsequent recovery. Nine out of eleven B/WF1 mice transplanted with semiallogeneic, BALB/c BM after TLI conditioning were stable chimeras without evidence of graft vs host disease and were permanently tolerant to BALB/c skin allografts in vivo and BALB/c alloantigens in vitro. BALB/c leads to B/WF1 chimeras showed BALB/c type in vitro proliferative mitogen responses without the age related decline in reactivity characteristic of untreated B/WF1. In contrast, adult B/WF1 mice were resistant to induction of completely allogeneic BM chimerism. The significance of these findings as they relate to the impaired immune status of female B/WF1 mice is discussed.