HIV-Specific Cd8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function

作者：Victor Appay, Douglas F. Nixon, Sean M. Donahoe, Geraldine M. Gillespie, Tao Dong, Abigail King, Graham S. Ogg, Hans Spiegel, Christopher P. Conlon, Celsa A. Spina, Diane V. Havlir, Douglas D. Richman, Anele Waters, Philippa Easterbrook, Andrew J. McMichael, Sarah Rowland‐Jones · 发表于：The Journal of Experimental Medicine · 年份：2000 · DOI：10.1084/jem.192.1.63 · 被引用次数：868 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、Cytomegalovirus and herpesvirus research

The use of peptide-human histocompatibility leukocyte antigen (HLA) class I tetrameric complexes to identify antigen-specific CD8(+) T cells has provided a major development in our understanding of their role in controlling viral infections. However, questions remain about the exact function of these cells, particularly in HIV infection. Virus-specific cytotoxic T lymphocytes exert much of their activity by secreting soluble factors such as cytokines and chemokines. We describe here a method that combines the use of tetramers and intracellular staining to examine the functional heterogeneity of antigen-specific CD8(+) T cells ex vivo. After stimulation by specific peptide antigen, secretion of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1beta, and perforin is analyzed by FACS((R)) within the tetramer-positive population in peripheral blood. Using this method, we have assessed the functional phenotype of HIV-specific CD8(+) T cells compared with cytomegalovirus (CMV)-specific CD8(+) T cells in HIV chronic infection. We show that the majority of circulating CD8(+) T cells specific for CMV and HIV antigens are functionally active with regards to the secretion of antiviral cytokines in response to antigen, although a subset of tetramer-staining cells was identified that secretes IFN-gamma and MIP-1beta but not TNF-alpha. However, a striking finding is that HIV-specific CD8(+) T cells express significantly lower levels of perfor...