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

We demonstrated that administration of interferon gamma (IFN-gama) to the inbred "l" strain of pregnant rats conferred partial resistance on their offspring to challenge with Trypanosoma cruzi. We now examine if this intervention 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 of recombinant rat IFN-gama, 50,000 IU/rat, five times/week for 3 weeks, which was started on the day of mating (IFN-Mo); infection with 106 trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gama treatment as given to the former group (TcIFN-Mo); the same protocol except that physiological saline was injected instead of IFN-gama (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 adjuvant-induced arthritic response or levels of major T cell subsets in spleen and lymph nodes. TcIFN-Mo and IFN-Mo offspring showed a reestablished arthritic response, which remained within the range seen in controls. Immunolabeling studies on parallel groups of 90-day-infected offspring showed that the inverse CD4/CD8 cell ratio that is usually seen in lymphoid organs from 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-gama is able to reverse the immunosuppressive state that is usually present during the chronic period of the experimental infection.

Efecto de la reinfeccion sobre la evalucion de ratas infectadas con Trypanosoma cruzi / Effect of reinfection on the evolution of rats infected with Trypanosoma cruzi

El objetivo de este trabajo fue comprobar si una de las variables medio-ambientales, la reinfeccion, puede modificar el comportamiento observado en un modelo de rata a nivel de parasitemia, anticuerpos sericos, manifestaciones electrocardiograficas y/o lesion miocardica. Los grupos experimentales fueron: GI: ratas infectadas al destete com 1 x "10 POT 6" T. cruzi; GR: igual a GI mas reinfecciones cada 30 dias hasta los 150 dias post-infeccion inicial (p.i.i.); "GI IND 1". Los xenodiagnosticos fueron negativos en los tres grupos. Los anticuerpos sericos no se modificaron significativamente en GR respecto de GI, salvo en los anticuerpos 7S, pues los del GR presentaron titulos superiores en algunos de los dias estudiados. Los ECG basales no mostraron cambios distintivos en las ratas infectadas. La pruieba de ajmalina mostro una disminucion de la FC independiente del tratamiento; el PR, QaT y QRS se prolongaron significativamente en todos los grupos respecto del basal (p < 0.05), salvo el QaT en el GT; ademas el cambio de PR y QaT fue mayor en los infectados (p < 0.05). En los grupos infectados hubo tambien una amplia variacion en la orientacion del eje electrico respecto del valor basal, acompanado de cambios morfologicos mas manifiestos emGR. La proporcion de lesion cardiaca detectada histologicamente en los grupos

Depressed adjuvant arthritis in rats transferred with spleen cells from Trypanosoma cruzi-infected syngeneic donors

In the present we investigated whether the attenuating effect of chronica Trypanosoma cruzi (Tc) infection on adjuvant arthritis (AA) in the rat could be transferred to naive recipients. Transfer of whole spleen cells, but not of serum, from Tc-infected rats reduced AA (x ñ SEM: 11 ñ 0.5) in recipient animals (control values, x ñ SEM: 19 ñ 0.7). Transfer of a T-cell enriched subpopulation from spleen cells of Tc-infected rats (obtained by filtration through a nylon column) resulted in a similar attenuationb of AA (x ñ SEM: 7.5 ñ 2.2). The arthritic response of rats intraperitoneally inoculated with 2 x 10**5 Tc 48h before induction did not differ from that observed in controls. Neither parasites nor specific antibodies were observed in suckling mice inoculated with serum or cell suspensions employed in transfer experiments. Consequently, the depressive effect on AA could not be directly attributed to Tc per se. We hypothesize that a homeostatic immunosuppressor mechanism may be responsible for this phenomenon