title: 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.
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.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Spiegel
authors.forename: G S
authors.initials: GS
authors.lastname: Ogg
authors.forename: E
authors.initials: E
authors.lastname: DeFalcon
authors.forename: M E
authors.initials: ME
authors.lastname: Sheehy
authors.forename: S
authors.initials: S
authors.lastname: Monard
authors.forename: P A
authors.initials: PA
authors.lastname: Haslett
authors.forename: G
authors.initials: G
authors.lastname: Gillespie
authors.forename: S M
authors.initials: SM
authors.lastname: Donahoe
authors.forename: H
authors.initials: H
authors.lastname: Pollack
authors.forename: W
authors.initials: W
authors.lastname: Borkowsky
authors.forename: A J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: D F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors