Role of HIV Envelope Proteins In Viral Replication and HIV Pathogenesis

National Institute Of Allergy And Infectious Diseases

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Abstract

In the past year we demonstrated that MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-beta, promote the differentiation of CD4+ T cells into alpha4beta7+CD69+CD103+ cells consistent with TRMs. We tested the ability of MAdCAM-1 to induce the differentiation of primary CD8+ cells into TRM. HIV-specific CD8+ TRM are present in HIV persistent sites such as gut tissues, lymph node and participate in immune surveillance and are correlated with HIV protection. Understanding the mechanisms involved in inducing CD8+ TRM will inform the development of anti-HIV-1 immune-based therapies and vaccine targeted to the mucosa. We developed a new method to induce freshly isolated CD8+ T cells to differentiate into multiple types of TRMs by stimulating primary CD8+ T cells with MAdCAM-1, the alpha4beta7 natural ligand, in the presence of retinoic acid (RA) and TGF-beta.