In:
Journal of Virology, American Society for Microbiology, Vol. 74, No. 16 ( 2000-08-15), p. 7320-7330
Abstract:
Although human immunodeficiency virus (HIV)-infected subjects without AIDS have a high frequency of HIV-specific CD8 T lymphocytes, cellular immunity is unable to control infection. Freshly isolated lymphocytes often do not lyse HIV-infected targets in 4-h cytotoxicity assays. A large fraction of circulating CD8 T cells from HIV-infected donors down-modulate CD3ζ, the signaling component of the T-cell receptor complex, which is reexpressed in vitro coincident with the return of cytotoxic function. To investigate further the link between CD3ζ down-modulation and possible CD8 T-cell functional defects, we used flow cytometry to characterize further the properties of the CD3ζ-down-modulated subset. HIV-specific CD8 T cells, identified by tetramer staining, are CD3ζ − . CD8 T cells with down-modulated CD3ζ also do not express the key costimulatory receptor CD28 and have the cell surface phenotype of activated or memory T cells (HLA-DR + CD62L − ). After T-cell activation, CD3ζ-down-modulated cells express the activation marker CD69 but not the high-affinity interleukin 2 (IL-2) receptor α-chain CD25 and produce gamma interferon but not IL-2. Therefore HIV-specific CD8 T cells have down-modulated key signaling molecules for T-cell activation and costimulation and require exogenous cytokine stimulation. The typical impairment of HIV-specific CD4 T helper cells, which would normally provide specific CD8 T-cell stimulation, means that in vivo CTL function in vivo is compromised in most HIV-infected individuals. In AIDS patients, the functional defect is more severe, since CD3ζ is not reexpressed even after IL-2 exposure.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.74.16.7320-7330.2000
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2000
detail.hit.zdb_id:
1495529-5
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