Naive human T cells develop into Th1 or Th0 effectors and exhibit cytotoxicity early after stimulation with Leishmania-infected macrophages

Studies of human disease suggest that naturally acquired immunity is the predominant outcome of Leishmania infection. Normally protective immune mechanisms activated during asymptomatic or self-healing infections may be minimal in patients who develop disease. To explore early immune responses, an in vitro model of human Leishmania infection was developed in which naive T cells were sensitized with Leishmania-infected macrophages. An analysis of Leishmania-specific cytokine production by these T cell lines revealed that most individuals developed Th1 or Th0 responses early after infection. Infected macrophages from Th1 responders produced interleukin-12. Th0 responders who produced little or no endogenous interleukin-12 could be converted to the Th1 phenotype by addition of interleukin-12 during priming. Finally, infection-sensitized T cells specifically lysed Leishmania-infected macrophages. Thus, this in vitro model system can be used to delineate protective human immune responses against Leishmania induced early after infection.