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Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-07-2103.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2711-2720
IMMUNOBIOLOGY
Expression of CD57 defines replicative senescence and
antigen-induced apoptotic death of CD8+ T cells
Jason M. Brenchley,
Nitin
J. Karandikar,
Michael R. Betts,
David R. Ambrozak,
Brenna J. Hill,
Laura E. Crotty,
Joseph P. Casazza,
Janaki Kuruppu,
Stephen A. Migueles,
Mark Connors,
Mario Roederer,
Daniel C. Douek, and
Richard 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.
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.
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