Early in vitro priming of distinct T-h cell subsets determines polarized growth of visceralizing Leishmania in macrophages

An in vitro priming system of murine naive splenocytes was established to i nvestigate early immune responses to Leishmania chagasi, the agent of visce ral leishmaniasis in the New World. Priming of splenocytes from resistant C 3H and CBA or susceptible BALE and B10 mice with L. chagasi resulted in bla st transformation and in proliferating parasite-specific CD4(+) T cells sec reting a differential complement of cytokines (IFN-gamma and low IL-10 leve ls for resistant T cells; IFN-gamma, IL-4 and high IL-10 levels for suscept ible T cells). After priming, intracellular parasite load was much higher i n susceptible than in resistant-type splenocyte cultures. On the other hand , infection of purified splenic macrophages from either resistant or suscep tible mice with live L, chagasi promastigotes, resulted in comparable paras ite loads, Moreover, when early CD4(+) T cell priming in splenocyte culture s was disrupted with anti-CD4 mAb, polarized parasite growth was abolished, becoming comparable in resistant and susceptible cultures. Neutralizing IL -4 activity during splenocyte priming did not affect the final parasite loa d in susceptible cultures. However, neutralizing IL-10 activity markedly de creased parasite load in susceptible, but not in resistant splenic macropha ges, These results suggest that IL-10 plays an important role in L. chagasi infection in susceptible hosts, The results also indicate that innate cont rol of growth of a visceralizing Leishmania in splenic macrophages results from the ability to activate different CD4(+) T cell subsets.