Persistent numbers of tetramer+ CD8(+) T cells, but loss of interferon-gamma+ HIV-specific T cells during progression to AIDS.
Although CD8(+) T cells initially suppress human immunodeficiency virus (HIV) replication, cytotoxic T-cell precursor frequencies eventually decline and fail to prevent disease progression. In a longitudinal study including 16 individuals infected with HIV-1, we studied both the number and function of HIV-specific CD8(+) T cells by comparing HLA-peptide tetramer staining and peptide-induced interferon-gamma (IFN-gamma) production. Numbers of IFN-gamma-producing T cells declined during progression to acquired immunodeficiency syndrome (AIDS), whereas the number of tetramer+ T cells in many individuals persisted at high frequencies. Loss of IFN-gamma-producing T cells correlated with declining CD4(+) T-cell counts, consistent with the need of CD4(+) T-cell help in maintaining adequate CD8(+) T-cell function. These data indicate that the loss of HIV-specific CD8(+) T-cell activity is not due to physical depletion, but is mainly due to progressively impaired function of HIV-specific CD8(+) T cells.
Kostense
Stefan
S
Department of Clinical Viro-Immunology, CLB/Sanquin Blood Supply Foundation, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
Vandenberghe
Kristin
K
Joling
Jeanine
J
Van Baarle
Debbie
D
Nanlohy
Nening
N
Manting
Erik
E
Miedema
Frank
F
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000595:Amino Acid Sequence; D001665:Binding Sites; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D018450:Disease Progression; D015693:Gene Products, nef / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency*; D008212:Lymphocyte Depletion; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D012044:Regression Analysis; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D006680:HLA Antigens; D010446:Peptide Fragments; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma