HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function
| Autor: | Douglas D. Richman, Victor Appay, Douglas F. Nixon, Diane V. Havlir, Hans M. L. Spiegel, Christopher P. Conlon, Philippa J. Easterbrook, Sarah Rowland-Jones, Graham S. Ogg, Abigail S. King, Geraldine M. Gillespie, Tao Dong, Celsa A. Spina, Andrew J. McMichael, Anele Waters, Sean M. Donahoe |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cytotoxic
T-Lymphocytes Cytomegalovirus HIV Infections CD8-Positive T-Lymphocytes Medical and Health Sciences Interleukin 21 0302 clinical medicine Reference Values Immunology and Allergy Cytotoxic T cell 2.1 Biological and endogenous factors IL-2 receptor Aetiology Chemokine CCL4 perforin 0303 health sciences biology virus diseases Macrophage Inflammatory Proteins Natural killer T cell Flow Cytometry 3. Good health Infectious Diseases tetramers Interleukin 12 HIV/AIDS Original Article Infection Immunology cytotoxic T lymphocytes Vaccine Related 03 medical and health sciences Interferon-gamma Clinical Research HIV Seronegativity Humans Antigen-presenting cell 030304 developmental biology Interleukin 3 CD40 Tumor Necrosis Factor-alpha Inflammatory and immune system Histocompatibility Antigens Class I HIV cytokines Clone Cells biology.protein 030215 immunology T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of experimental medicine, vol 192, iss 1 The Journal of Experimental Medicine |
| DOI: | 10.1084/jem.192.1.63 |
| Popis: | 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 perforin than CMV-specific CD8(+) T cells. This lack of perforin is linked with persistent CD27 expression on HIV-specific cells, suggesting impaired maturation, and specific lysis ex vivo is lower for HIV-specific compared with CMV-specific cells from the same donor. Thus, HIV-specific CD8(+) T cells are impaired in cytolytic activity. |
| Databáze: | OpenAIRE |
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