Regulation of the immune response in experimental models of autoimmune disorders. II. Induction of suppressor cells of the mixed lymphocyte culture in adult (NZB x NZW)F1 mice using total lymphoid irradiation.

Kinetic studies were done on mixed lymphocyte reaction suppressor cells generated in female (NZB x NZW)F1 hybrid mice (B/WF1) treated with total lymphoid irradiation (TLI) and in stable BALB/c leads to B/WF1 bone marrow chimeras prepared with TLI (8 daily fractions of 200 rads followed by either whole body irradiation 400 rads (WBI) or intravenous cyclophosphamide (CY) 100--200 mg/kg). All chimeras maintained intact BALB/c skin grafts (greater than 500 days) and showed no signs of graft vs host disease (GVHD). Radioresistant alloantigen-nonspecific suppressor cells were apparent in the spleen immediately following TLI (78--88% suppression of 3H-thymidine incorporation by co-cultured spleen cells using unrelated stimulator and responder cells in one way MLR). The suppressive capacity was of a relatively short duration since suppression became inapparent within 15--30 days following TLI. Nonspecific radioresistant suppressor cells were maintained in stable BALB/c leads to B/WF1 chimeras for longer periods of time (7 months in chimeras prepared with TLI and CY and 11 months of chimeras prepared with TLI and WBI). On the other hand, specific suppressor cells blocking host type (B/WF1 chimeras. The data suggest that the impaired suppressive immunoregulatory functions of B/WF1 mice can be corrected by normal stem cells even though maturation occurs in the B/WF1 lymphoid milieu.