Cellular Immunity in HIV-1 Infected Individuals in India

$242,460P30FY2005AINIH

Emory University, Atlanta GA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Current research suggests that cellular immunity, in particular anti-viral CD8 T cells, play a pivotal role in maintaining effective control of viral replication in HIV-infected individuals. Studies employing CD8 depletions in macaques clearly demonstrate a central role for anti-viral CD8 T cells in controlling immunodeficiency virus infections. However, HIV-infected patients can experience persistent, unabated viral replication and disease progression despite the presence of robust CD8 T cell responses. Thus, recent focus has shifted to studies on the quality as well as the magnitude of anti-viral CD8 T cells. Indeed, HIV-specific CD8 T cells can undergo skewed maturation and have a defective proliferative capacity with compromised perforin expression. Ongoing studies in our laboratory as well as studies from other laboratories strongly suggest a critical role for IFN-gamma plus IL-2 producing T cells for the control immunodeficiency virus infections in humans and macaques. Our results also demonstrate that highly active anti-retroviral therapy (HAART) can improve the frequency of IFNgamma plus IL-2 producing CD4 T cells in a time dependent manner. However, essentially there are no data available on the magnitude and quality of HIV-specific CD4 and CD8 T cells in HAART naive and treated individuals living in developing countries such as India where the burden of opportunistic infections that can influence the quality of HIV-specific T cells is very high. The overall goal of this supplement is to increase the sustainable research capacity of India in state-of-the-art immunology assays and evaluate the effect of viremia and HAART on the magnitude and quality of HIV-specific T cells in HIV-infected individuals in India. The information that we generate from these studies will be a valuable resource for the scientific community in India for the development of effective vaccines for HIV/AIDS. [unreadable] [unreadable]

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