Vgamma2Vdelta2 T cell recognition of HIV-infected cells in the lung

University Of Maryland Baltimore, Baltimore MD

Investigators

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Abstract

? DESCRIPTION (provided by applicant): Cardiopulmonary disease is a leading cause of death for HIV patients in the US. Chronic inflammation and immunodeficiency persist even during effective anti-retroviral therapy and virus suppression. Eliminating latent infection is a major barrier to reducing co-morbidity, eradicating HIV and achieving a cure for AIDS. HIV viremia results in extensive depletion of effector ?? T cells and reduces patients' ability to combat co-infections and chronic inflammation. Gammadelta T cells, activated by clinically approved bisphosphonate agents, recognize and kill HIV-infected T cells, as well as inflammatory macrophages, through direct or indirect cytolysis. We found that activated ?? T cells also have the capacity to recognize and kill latently infected cells with little or no active virus replicatin. Immunotherapy targeting ?? T cells may help treat the chronic inflammation seen in HIV-associated cardiopulmonary disease, in addition to eradicating latent infection. Our aims are to define ?? T cell surface receptors and target cell ligands involved in recognitio of latently infected cells and test strategies for improving target cell destruction. Clinical trias for cancer immunotherapy test the anti-tumor properties of ?? T cell expansion after bisphosphonate plus IL-2 therapy. In Aim I, we use this immunotherapy strategy to test for ?? T cell cytotoxicity against latently infected CD4 T cell targets and characterize the mechanisms of recognition. In Aim II, we evaluate the ?? T cell deficiencies in cytotoxic recognition seen in HV infection. In Aim III, we test strategies to further improve ?? T cell recognition and killing of latently infected targets. This pilot study will test the ability to exploit the unique capacities f ?? T cells to kill infected HIV cells, which may be achieved with approved drugs, and seek to eradicate the viral reservoir and provide a functional cure for AIDS.