[No Title Available]

Abstract

immunopathogenesis of murine visceral leishmaniasis (VL), but a functional link between these two pathways is unknown. Here, we investigated a direct link between CTLA-4 downregulation of CD4 + T cell responses and TGF-β secretion in murine VL.Activation of CD4 + T cells from VL leads to intense CTLA-4 mediated TGF-β production, as assessed either by CTLA-4 blockade, or by direct CTLA-4 crosslinkage. Intracellular growth of Leishmania chagasi in cocultured splenic macrophages was dependent on both CTLA-4 function and TGF-β secretion. Crosslinkage of CTLA-4 markedly increased L. chagasi replication and this effect could be completely blocked with neutralizing anti-TGF-β. Addition of rTGF-β1 restored parasite growth in cultures protected from parasitism by CTLA-4 blockade. Anti-TGF-β failed to increase IL-2 production, but markedly increased IFN-γ production by CD4 + T cells. Our findings indicate that parasite persistence in murine VL depends on CTLA-4 mediated TGF-β production by CD4 + T cells. Resistance to leishmania infection is mediated by cellular immune response, characterized by IFN-γ activated macrophage killing of leishmania. Different from visceral leishmaniasis (VL), patients with tegumentary leishmaniasis usually have a strong T cell response to Leishmania antigen. Such response is caracterized by delayed-type hipersensitivity, IFN-γ and IL-2 production in vitro by antigen stimulated peripheral blood mononuclear cells (PBMC). Tegumentary leishmaniasis have a spectrum of diseases, including anergic diffuse cutaneous leishmaniasis (DCL), and the responsives forms of mucosal leishmaniasis (MCL), disseminated cutaneous leishmaniasis and the localized cutaneous leishmaniasis (CL) (GRIMALDI et al., 1993). Supported by: CAPES, CNPq, FAPERJ, PADCT, PRONEX-MCT IM-2 -EVALUATION OF IMMUNE RESPONSES OF SUBCLINIC INDIVIDUALS INFECTED BY L. BRAZILIENSIS, LIVING AN ENDEMIC AREA OF CUTANEOUS LEISHMANIASISThe aim of the present study was to characterize the immune responses of individuals with subclinical form of tegumentary leishmaniasis, characterized by positive intradermal skin test and no sign of disease or previous scar. The Mean ± SE of stimulation indices of proliferative responses in PBMC stimulated by leishmania antigen (2mg) of these subclinical was 12,6 ± 3,7. The levels of IFN-γ and TNF-α in antigen stimulated PBMC from individuals with subclinical form of tegumentary leishmaniasis was significantly lower than the ones from CL patients (296,0 ± 119,6 pg/ml versus 1549,5 ± 283,9 pg/ml and 55,0 ± 20,4 pg/ml versus 258,9 ± 65,1 pg/ml for IFN-γ and TNF-α, respectively; p < 0,001, Mann Whitney). IL-5 levels in antigen stimulated PBMC from individuals with subclinical form of tegumentary leishmaniasis were higher than the ones from CL patients (105,7 ± 31,6 pg/ml versus 31,8 ± 9,7 pg/ml, respectively; p = 0.1392, Mann Whitney). Previous publications have shown that IFN-γ is important in control parasite multiplication. However, an excess of IFN-γ production could up regulate TNF-α production, leading to the ti...