Estudo Funcional de Células T CD4+ expressando distintas regiões V beta do receptor de célula T (TCR) em pacientes com Leishmaniose cutânea

Abstract

Leishmaniasis is an endemic parasitic disease affecting 12 million worldwide. The establishment of an effective immune response directed against Leishmania is critical for the disease control. An important approach in the study of the immune response is evaluating host-parasite interaction. Different immune responses elicited by parasite infection can be directly related to distinct effector T cell subpopulations expressing specific TCR. To better understand the role that subpopulations of CD4+ T cells expressing distinct Vb usage may have in the human immune response against Leishmania braziliensis, a detailed study defining the activation state and the cytokine profile was performed with a group of well-defined cutaneous leishmaniasis patients and a group of normal individuals. Using flow cytometry, we evaluated in vitro the frequency of T CD4+ cells expressing the following V: V 2, 3, 5.1, 5.2, 8, 11, 12, 17 and 24 in the different groups. The frequency of Vb positive, CD4+ within CD4+ T cells was calculated without stimulus, as well as after culture with soluble Leishmania antigen (SLA). Our results show that: (1) CD4+ T cells expressing distinct Vb usage, increased expression of Vb 5.2 and V 24 in cutaneous leishmaniasis as compared with normal individuals; (2) cutaneous leishmanisis patients demonstrate and increase in CD4+ T cells expressing Vb 5.2, 11, 12 and 17, after stimulus with SLA; (3) Distinct populations of Vb expressing CD4+ T cells are found to expressing activation markers (HLA-DR), memory markers (CD45RO), as well as pro-inflammatory (IFN-g, TNF-a), and anti-inflammatory (IL-10), cytokines after stimulus with SLA; (4) Positive correlations between CD4+ T cells expressing Vb 5.2, 11 and 17, producing pro-inflammatory (IFN-g, TNF-a), and anti-inflammatory (IL-10), cytokines are seen after stimulus with SLA. Given that cutaneous leishmaniasis is a form of leishmaniasis that is often followed by spontaneous cure, the activation of specific subpopulations during this disease could allow the formation of an effective cellular response. This study might lead us to the discovery of immunodominant Leishmania antigens important for triggering efficient host responses against the parasite.