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International Immunology, Vol. 12, No. 9, 1227-1233, September 2000
© 2000 Japanese Society for Immunology

Early in vitro priming of distinct Th cell subsets determines polarized growth of visceralizing Leishmania in macrophages

Nitza A. Gomes, Victor Barreto-de-Souza and George A. DosReis

Immunobiology Program, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Ilha do Fundão, Rio de Janeiro, RJ 21944-970, Brazil

Correspondence to: G. A. DosReis

An in vitro priming system of murine naive splenocytes was established to investigate early immune responses to Leishmania chagasi, the agent of visceral leishmaniasis in the New World. Priming of splenocytes from resistant C3H and CBA or susceptible BALB and B10 mice with L. chagasi resulted in blast transformation and in proliferating parasite-specific CD4+ T cells secreting a differential complement of cytokines (IFN-{gamma} and low IL-10 levels for resistant T cells; IFN-{gamma}, IL-4 and high IL-10 levels for susceptible T cells). After priming, intracellular parasite load was much higher in susceptible than in resistant-type splenocyte cultures. On the other hand, infection of purified splenic macrophages from either resistant or susceptible mice with live L. chagasi promastigotes, resulted in comparable parasite loads. Moreover, when early CD4+ T cell priming in splenocyte cultures 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 load in susceptible cultures. However, neutralizing IL-10 activity markedly decreased parasite load in susceptible, but not in resistant splenic macrophages. These results suggest that IL-10 plays an important role in L. chagasi infection in susceptible hosts. The results also indicate that innate control of growth of a visceralizing Leishmania in splenic macrophages results from the ability to activate different CD4+ T cell subsets.

Keywords: cytokines, differentiation, IL-10, Leishmania, Th1/Th2, visceral leishmaniasis

Transmitting editor: R. L. Coffmann


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