LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8 T Cells after Heterologous Prime-Boost Vaccination against Infection.

Integrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as , the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8 T cells generated by heterologous prime-boost immunization during experimental infection with . To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules. After anti-LFA-1, but not anti-VLA-4 treatment, all vaccinated mice displayed increased blood and tissue parasitemia, and quickly succumbed to infection. In addition, there was an accumulation of specific CD8 T cells in the spleen and lymph nodes and a decrease in the number of those cells, especially in the heart, suggesting that LFA-1 is important for the output of specific CD8 T cells from secondary lymphoid organs into infected organs such as the heart. The treatment did not alter CD8 T cell effector functions such as the production of pro-inflammatory cytokines and granzyme B, and maintained the proliferative capacity after treatment. However, the specific CD8 T cell direct cytotoxicity was impaired after LFA-1 blockade. Also, these cells expressed higher levels of Fas/CD95 on the surface, suggesting that they are susceptible to programmed cell death by the extrinsic pathway. We conclude that LFA-1 plays an important role in the migration of specific CD8 T cells and in the direct cytotoxicity of these cells.