KINETIC-ANALYSIS OF ANTIGEN-SPECIFIC IMMUNE-RESPONSES IN RESISTANT AND SUSCEPTIBLE MICE DURING INFECTION WITH TRYPANOSOMA-CRUZI

The Tulahuen strain of Trypanosoma cruzi has been shown previously to cause higher parasitemias and greater mortality in BALB/c mice compare d with C57BL6/J mice. The goal of our study was to determine whether d ifferent cytokine responses to parasite Ag during T. cruzi infection c orrelate with the susceptible and resistant phenotypes identified in t hese mice. At several time points after initial infection with insect- derived metacyclic trypomastigotes, lymph node and spleen cell suspens ions were prepared from animals of each mouse strain. These lymphocyte suspensions were stimulated with Ag prepared from cultured parasites and the production of IFN-gamma, IL-4, IL-2, and IL-5 was measured. Ly mphocytes from C57BL6/J mice produced 10-fold more IFN-gamma than BALB /c lymphocytes. However, this enhanced response occurred only for a li mited time preceding peak parasitemias. Ag-induced secretion of IL-4 f rom BALB/c lymphocytes was detectable by 2 wk of infection and increas ed during the 2nd and 3rd mo of infection. Most C57BL6/J culture super natants did not contain measurable leveLs of IL-4. Lymphocytes from bo th murine strains produced levels of IL-2 and IL-5 indistinguishable f rom uninfected controls. These results indicate that increased numbers or potency of lymphocytes that produce Ag-specific IFN-gamma response s are present in resistant mice during T. cruzi infection. This phenom enon may he responsible for the lower parasitemias seen in C57BL6/J mi ce. However, even these relatively resistant mice become chronically i nfected with T. cruzi, and spleen cells from infected mice can suppres s IFN-gamma induced by heterologous Ag. Our data suggest that IL-4 pro duction is a marker for the T. cruzi susceptible phenotype. Differenti al production of IL-2 or IL-5 was not found, suggesting that these cyt okines are not important factors in T. cruzi resistance or susceptibil ity.