Abstract
CD8+ T cells play a key role in protective immunity against intracellular pathogens, such as Trypanosoma cruzi, the causative agent of Chagas disease. Integrins, cell adhesion molecules (CAM) and chemokine receptors may play a critical role in this process allowing these cells migrate to non-peripheral lymphoid tissues to exert their effector function. Recently, we demonstrated that treatment with the drug FTY720, an immunomodulator that acts as a high-affinity agonist at the sphingosine 1-phosphate receptor-1 (S1P1) that inhibits the cell traffic an exit from lymph nodes (LN), led to retention of specific CD8+ T cells in both LN of C57BL/6 mice infected as in A/Sn mice vaccinated and infected, making them susceptible to infection. These results were the first experimental evidence that the recirculation of specific CD8+ T cells is important for effectuation the immune response in T. cruzi infection model (Domingues et al., 2012). In analysis of cell surface molecules specific CD8+ T cells generated by genetic vaccination with T. cruzi ASP-2, amastigote surface protein-2, we found increased expression of molecules LFA-1 and VLA-4 in these cells (Vasconcelos et al., 2012). In view of this, the overall goal of this project is to study the role of the integrins LFA-1 and VLA-4, CAM ICAM-1 and the chemokine receptors CCR5, CXCR3 and CXCR4 in the migration of CD8+ cells generated by specific genetic immunization with heterologous ASP-2 T. cruzi. To do so, we will treat these immunized and infected mice with antibodies in order to block these molecules and observe whether an increasing in susceptibility may occur. This study is very important for the development of vaccines in general, and if it can in fact occur demonstrates the importance of migration of T lymphocytes, and molecules that mediate this process on the immunity induced by vaccination of experimental heterologous prime-boost. (AU)
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