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Journal of Virology, January 2000, p. 1018-1022, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4+ T Cells

Hans M. L. Spiegel,1 Graham S. Ogg,2 Elizabeth DeFalcon,1 Megan E. Sheehy,1 Simon Monard,1 Patrick A. J. Haslett,3 Geraldine Gillespie,2 Sean M. Donahoe,1 Henry Pollack,4 William Borkowsky,4 Andrew J. McMichael,2 and Douglas F. Nixon1,*

Aaron Diamond AIDS Research Center, The Rockefeller University,1 and Division of Pediatric Infectious Diseases, New York University Medical Center,4 New York, New York 10016; Molecular Immunology Group, Nuffield Department of Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom2; and Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021-63993

Received 28 May 1999/Accepted 19 October 1999

CD4+ T cells are thought to be critical in the maintenance of virus-specific CD8+ cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4+ T-cell count decreases has been reported. Using HLA-peptide tetrameric complexes, we show the presence at high frequency of HIV-1- and cytomegalovirus-specific CD8+ T cells when the peripheral CD4+ T-cell count was low or zero in three HIV-1-infected patients. No direct virus-specific CD8+-mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitro in the presence of interleukin-2 into responsive effector cells. Thus, virus-specific CD8+ T cells can be maintained in the peripheral circulation at high frequency in the absence of circulating peripheral CD4+ T cells, but these cells may lack direct effector activity. Strategies designed to overcome this antigen unresponsiveness may be of value in therapies for the treatment of AIDS.

* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Ave., New York, NY 10016. Phone: (212) 448-5010. Fax: (212) 725-1126. E-mail: DNixon{at}ADARC.org.

Journal of Virology, January 2000, p. 1018-1022, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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