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Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2000, Vol. 96, No. 9, pp. 3094-3101 IMMUNOBIOLOGY Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection Premlata Shankar, Melissa Russo, Brooke Harnisch, Mark Patterson, Paul Skolnik, and Judy Lieberman From the Center for Blood Research, Harvard Medical School, and the New England Medical Center, Tufts University School of Medicine, Boston, MA. The functional status of circulating human immunodeficiency (HIV)-specific CD8 T cells in chronically infected subjects was evaluated. By flow cytometry, only 5 of 7 subjects had detectable CD8 T cells that produced IFN- after stimulation with HIV-infected primary CD4 T cells. In 2 subjects, the frequency of IFN--producing cells increased 4-fold when IL-2 was added to the culture medium; in another subject, IFN--producing cells could be detected only after IL-2 was added. IFN--producing cells ranged from 0.4% to 3% of CD8 T cells. Major histocompatibility complex-peptide tetramer staining, which identifies antigen-specific T cells irrespective of function, was used to evaluate the proportion of HIV-specific CD8 T cells that may be nonfunctional in vivo. CD8 T cells binding to tetramers complexed to HIV gag epitope SLYNTVATL and reverse transcriptase epitope YTAFTIPSI were identified in 9 of 15 and 5 of 12 HLA-A2-expressing seropositive subjects at frequencies of 0.1% to 1.1% and 0.1 to 0.7%, respectively. Freshly isolated tetramer-positive cells expressed a mixed pattern of memory and effector markers. On average, IFN- was produced by less than 25% of tetramer-positive CD8 T cells after stimulation with the relevant gag or reverse transcriptase peptide. In all subjects tested, freshly isolated CD8 T cells were not cytolytic against peptide-pulsed B lymphoblastoid cell line or primary HIV-infected CD4 T-cell targets. Exposure to IL-2 enhanced the cytotoxicity of CD8 T cells against primary HIV-infected CD4 targets in 2 of 2 subjects tested. These results suggest that a significant proportion of HIV-specific CD8 T cells may be functionally compromised in vivo and that some function can be restored by exposure to IL-2. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. J. Chang, S. Sirivichayakul, A. Avihingsanon, A. J. V. Thompson, P. Revill, D. Iser, J. Slavin, S. Buranapraditkun, P. Marks, G. Matthews, et al. Impaired Quality of the Hepatitis B Virus (HBV)-Specific T-Cell Response in Human Immunodeficiency Virus Type 1-HBV Coinfection J. Virol., August 1, 2009; 83(15): 7649 - 7658. 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