Journal article
Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells
Blood, Vol.101(7), pp.2711-2720
04/01/2003
DOI: 10.1182/blood-2002-07-2103
PMID: 12433688
Abstract
Virus-specific CD8+ T-cell responses play a pivotal role in limiting viral replication. Alterations in these responses, such as decreased cytolytic function, inappropriate maturation, and limited proliferative ability could reduce their ability to control viral replication. Here, we report on the capacity of HIV-specific CD8+ T cells to secrete cytokines and proliferate in response to HIV antigen stimulation. We find that a large proportion of HIV-specific CD8+ T cells that produce cytokines in response to cognate antigen are unable to divide and die during a 48-hour in vitro culture. This lack of proliferative ability of HIV-specific CD8+ T cells is defined by surface expression of CD57 but not by absence of CD28 or CCR7. This inability to proliferate in response to antigen cannot be overcome by exogenous interleukin-2 (IL-2) or IL-15. Furthermore, CD57 expression on CD8+ T cells, CD4+ T cells, and NK cells is a general marker of proliferative inability, a history of more cell divisions, and short telomeres. We suggest, therefore, that the increase in CD57+ HIV-specific CD8+ T cells results from chronic antigen stimulation that is a hallmark of HIV infection. Thus, our studies define a phenotype associated with replicative senescence in HIV-specific CD8+ T cells, which may have broad implications to other conditions associated with chronic antigenic stimulation.
Details
- Title: Subtitle
- Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells
- Creators
- Jason M Brenchley - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasNitin J Karandikar - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasMichael R Betts - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasDavid R Ambrozak - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasBrenna J Hill - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasLaura E Crotty - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasJoseph P Casazza - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasJanaki Kuruppu - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasStephen A Migueles - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasMark Connors - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasMario Roederer - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasDaniel C Douek - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, DallasRichard A Koup - From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, Dallas
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.101(7), pp.2711-2720
- DOI
- 10.1182/blood-2002-07-2103
- PMID
- 12433688
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 04/01/2003
- Academic Unit
- Pathology
- Record Identifier
- 9984047644402771
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