Resistance of BALB/c mice to Leishmania major infection is associated with a decrease in the precursor frequency of antigen-specific CD4+ cells secreting interleukin-4

BALB/c mice are highly susceptible to infection with the protozoanparasite Leishmania major and develop a chronic fatal disease.They can, however, be manipulated to resist disease and thishas been shown to correlate with increased expression of IFN_–mRNA and the absence of IL-4 mRNA in the draining lymph nodesand spleens of these animals. Here we show that anti-IL-4 oranti-CD4 treatment of BALB/c mice resulted in a reduction inthe size of the lesion and in the number of parasites in thedraining lymph nodes compared with untreated mice. The precursorfrequency of CD4⁺ T cells proliferating in response to Leishmaniaantigens in vitro in the treated animals was not significantlydifferent from untreated animals. Analysis of the lymphokinessecreted by the clonal progeny of these cells showed that theprecursor frequency of IL-4 secreting clones was at least 10-foldlower in animals treated with either mAb. However, there wasno reciprocal increase in the precursor frequencies of IFN_–secreting clones. Comparisons of the total number of precursorsof specific CD4⁺ cells secreting IFN_– showed that anti-CD4-treatedanimals, which are resistant to disease, had considerably fewerfor the first 6 weeks than untreated mice with chronic disease.Protection of BALB/c mice was therefore associated with a reductionin the numbers of precursors of cells secreting IL-4 withouta concomitant increase in the number of precursors of IFN_–secreting cells.