Over the past 2 years, a clearer picture has emerged regarding the properties of HIV-specific CD8+ T cells associated with immunologic control of HIV replication. These properties represent a potential mechanism by which rare patients might control HIV replication in the absence of antiretroviral therapy. This review addresses the background and recent findings that have lead to our current understanding of these mechanism(s).
Patients with immunologic control of HIV are not distinguished by targeted specificities, or greater numbers or breadth of their HIV-specific CD8+ T-cell response. For this reason, recent work has focused greater attention on qualitative features of this response. The qualitative features most closely associated with immunologic control of HIV are related to the granule-exocytosis-mediated elimination of HIV-infected CD4+ T cells. The ability of HIV-specific CD8+ T cells to increase their contents of proteins known to mediate cytotoxicity, such as granzyme B and perforin, appears to be a critical means by which HIV-specific cytotoxic capacity is regulated.
Investigation from multiple groups has now focused upon HIV-specific CD8+ T-cell granule-exocytosis-mediated cytotoxicity as a correlate of immunologic control of HIV. In the near future, a more detailed understanding of the qualities associated with immunologic control may provide critical insights regarding the necessary features of a response that should be stimulated by immunotherapies or T-cell-based vaccines.
aDepartment of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
bHIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Correspondence to Mark Connors, LIR, NIAID, NIH, Building 10, Room 11B-09, 10 Center Dr. MSC 1876, Bethesda, MD 20892-1876, USA Tel: +1 301 496 8057; fax: +1 301 402 0070; e-mail: email@example.com