Administration of interferon-g to pregnant rats reverses the depressed adjuvant-induced arthritis of their chronically Trypanosoma cruzi-infected offspring

We demonstrated that administration of interferon gamma (IFN-gamma) to the inbred "1" strain of pregnant rats conferred partial resistance on their of fspring to challenge with Trypanosoma cruzi. We now examine if this interve ntion also modifies the reportedly immunodepressed cellular responses which occur during chronic infection. Offspring were born to mothers undergoing one of the following procedures during gestation: subcutaneous injections o f recombinant rat IFN-gamma, 50,000 IU/rat, five times/week for 3 weeks, wh ich was started on the day of mating (IFN-Mo); infection with 10(6) trypoma stigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gamma trea tment as given to the former group (TcIFN-Mo); the same protocol except tha t physiological saline was injected instead of IFN-gamma (Tc-Mo); injection of physiological saline only (control-Mo). All offspring groups (N = 8-10/ group) were infected at weaning and were assessed 90 days later for their a djuvant-induced arthritic response or levels of major T cell subsets in spl een and lymph nodes. TcIFN-Mo and IFN-Mo offspring showed a reestablished a rthritic response, which remained within the range seen in controls. Immuno labeling studies on parallel groups of 90-day-infected offspring showed tha t the inverse CD4/CD8 cell ratio that is usually seen in lymphoid organs fr om these chronically infected rats (median 0.61) appeared to have recovered in the TcIFN-Mo and IFN-Mo groups (median 1.66 and 1.78, respectively) and was not different from uninfected controls (1.96). These studies indicate that early stimulation with IFN-gamma is able to reverse the immunosuppress ive state that is usually present during the chronic period of the experime ntal infection.