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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

2000; American Society for Microbiology; Volume: 74; Issue: 2 Linguagem: Inglês

10.1128/jvi.74.2.1018-1022.2000

1098-5514

Hans Spiegel, Graham S. Ogg, Elizabeth DeFalcon, Megan E. Sheehy, Simon Monard, Patrick Haslett, Geraldine M. Gillespie, Sean M. Donahoe, Henry Pollack, William Borkowsky, Andrew J. McMichael, Douglas F. Nixon,

Cytomegalovirus and herpesvirus research

ABSTRACT 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.