Immunoregulation in leishmaniasis

RESUMO

Leishmaniasis is caused by protozoa of the genus Leishmania which are transmitted to humans by the bite of infected phlebotomine sandflies. Four different clinical forms of leishmaniasis are well characterized cutaneous leishmaniasis, mucosal leishmaniasis, diffuse cutaneous leishmaniasis and visceral leishmaniasis. Recovery from and resistance to disease in leishmaniasis are strongly associated to effective T cell responses, with no recognized participation of specific antibodies. Protective immunity against Leishmania has been related, predominantly, to IFN-gamma producing CD4+ Th1 helper T cells. IFN-gamma is known as the macrophage activating factor and addition of this cytokine to Leishmania-infected macrophages results in Leishmania killing. There are also indications of the participation of cytotoxic CD8+ T cells in the control of Leishmania infection. The immunological responses are different in the clinical forms of leishmaniasis. Patients with visceral leishmaniasis have absence of lymphocyte proliferative response and IFN-gamma production upon leishmanial antigen stimulation, and there is mRNA for IL-10 and IL-4 in peripheral blood mononuclear cells. In the present study it is documented that lymphocyte proliferation and IFN-gamma production are restored by addition to the cultures of either nonoclonal antibody anti-IL-10 or IL-12. These data are evidence of Th2 activation in visceral leishmaniasis and indicate that cytokine or cytokine antagonists may be used as therapeutic adjuvants in visceral leishmaniasis. Different from visceral leishmaniasis, patients with cutaneous or mucosal leishmaniasis have a strong T cell response to leishmania antigen. Such response is characterized by delayed type hypersensitivity, lymphocyte proliferation and production of cytokines such as IL-2 and IFN-gamma. In this study the cytotoxic response in patients with tegumentary leishmaniasis was documented by the ability of PBMC from cutaneous and mucosal leishmaniasis patients to kill K562 tumor target cells. Moreover the ability of cytokine and cytokine antagonist in modulating cytotoxic functions was tested. Evidence was found that antigen-induced cytotoxicity against K562 tumor target cell was modulated by both IL-10 and TGF-beta. When L.amazonensis antigen stimulated patient PBMC were tested in the presence of TGF-beta there was a marked reduction in the cytotoxicity against K562...