Differences in gamma interferon production in vitro predict the pace of the in vivo response healthy to Leishmania amazonensis in healthy volunteers

The initial encounter of Leishmania cells and cells from the immune system is fundamentally important in the outcome of infection and determines disea se development or resistance. We evaluated the anti-Leishmania amazonensis response of naive volunteers by using an in vitro priming (IVP) system and comparing the responses following in vivo vaccination against the same para site. In vitro stimulation allowed us to distinguish two groups of individu als, those who produced small amounts of gamma interferon (IFN-gamma) (n = 16) (low producers) and those who produced large amounts of this cytokine ( n = 16) (high producers). IFN-gamma production was proportional to tumor ne crosis factor alpha and interleukin 10 (IL-10) levels but did not correlate with IL-5 production. Volunteers who produced small amounts of IFN-gamma i n vitro remained low producers 40 days after vaccination, whereas high prod ucers exhibited increased IFN-gamma production. However, 6 months after vac cination, all individuals tested produced similarly high levels of IFN-gamm a upon stimulation of their peripheral blood mononuclear cells with Leishma nia promastigotes, indicating that low in vitro producers respond slowly in vivo to vaccination. In high IFN-gamma producers there was an increased fr equency of activated CD8(+) T cells both in vitro and in vivo compared to t he frequency in low producers, and such cells were positive for IFN-gamma a s determined by intracellular staining. Such findings suggest that IVP resp onses can be used to predict the pace of postvaccination responses of test volunteers. Although all vaccinated individuals eventually have a potent an ti-Leishmania cell-mediated immunity (CMI) response, a delay in mounting th e CMI response may influence resistance against leishmaniasis.