Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response toLeishmania amazonensisin Healthy Volunteers

Abstract

The initial encounter of Leishmania cells and cells from the immune system is fundamentally important in the outcome of infection and determines disease 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 parasite. In vitro stimulation allowed us to distinguish two groups of individuals, those who produced small amounts of gamma interferon (IFN-γ) (n = 16) (low producers) and those who produced large amounts of this cytokine (n = 16) (high producers). IFN-γ production was proportional to tumor necrosis factor alpha and interleukin 10 (IL-10) levels but did not correlate with IL-5 production. Volunteers who produced small amounts of IFN-γ in vitro remained low producers 40 days after vaccination, whereas high producers exhibited increased IFN-γ production. However, 6 months after vaccination, all individuals tested produced similarly high levels of IFN-γ upon stimulation of their peripheral blood mononuclear cells with Leishmania promastigotes, indicating that low in vitro producers respond slowly in vivo to vaccination. In high IFN-γ producers there was an increased frequency of activated CD8+ T cells both in vitro and in vivo compared to the frequency in low producers, and such cells were positive for IFN-γ as determined by intracellular staining. Such findings suggest that IVP responses can be used to predict the pace of postvaccination responses of test volunteers. Although all vaccinated individuals eventually have a potent anti-Leishmania cell-mediated immunity (CMI) response, a delay in mounting the CMI response may influence resistance against leishmaniasis

Leukotrienes Are Essential for the Control ofLeishmania amazonensisInfection and Contribute to Strain Variation in Susceptibility

“…Differences in the generation of IL-10 (32, 33), TFG-␤ (34), and NO (35), and in the response to IL-12 (5) and IFN-␥ (36,37), have all been suggested. However, no previous reports have considered the role of lipid mediators in the resistance and susceptibility to infection.…”

B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniases

“…Expansion of CD8 + T cells occurs in the peripheral blood of individuals vaccinated against leishmaniasis (Mendonça et al 1995, Gurunathan et al 2000. Especially, the percentage of activated CD8 + T cells was higher in fast responding than in slow responding volunteers to vaccination (Pompeu et al 2001).The role of B cells in leishmaniasis is also not clear. High antibody levels are present in the more severe clinical form of the cutaneous disease, namely diffuse cutaneous leishmaniasis (DCL) (Schurr et al 1986, Mengistu et al 1990), but B cell depletion does not alter the susceptibility or resistance pattern to Leishmania infection in mice (Babai et al 1999, Brown & Reiner 1999.…”

“…Expansion of CD8 + T cells occurs in the peripheral blood of individuals vaccinated against leishmaniasis (Mendonça et al 1995, Gurunathan et al 2000. Especially, the percentage of activated CD8 + T cells was higher in fast responding than in slow responding volunteers to vaccination (Pompeu et al 2001).…”

Importance of CD8 T cell-mediated immune response during intracellular parasitic infections and its implications for the development of effective vaccines

“…When re-stimulated in vitro with Leishmania antigens, human CD8 T cells secrete IFN-γ , an important mediator of resistance against certain types of infection with Leishmania sp (De Luca et al 1999, Bottrel et al 2001, Pompeu et al 2001. Also, in individuals that develop the mucocutaneous form of the disease, CD8 T lymphocytes are highly cytolytic in vitro against Leishmania-infected macrophages (Brodskyn et al 1997).…”