An antigenic threshold for maintaining human immunodeficiency virus type 1-specific cytotoxic T lymphocytes

被引:27
作者
Jin, X
Ogg, G
Bonhoeffer, S
Safrit, J
Vesanen, M
Bauer, D
Chen, D
Cao, YZ
Demoitie, MA
Zhang, LQ
Markowitz, M
Nixon, D
McMichael, A
Ho, DD
机构
[1] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA
[2] Inst Mol Med, Oxford, England
[3] Fredrich Miescher Inst, Basel, Switzerland
[4] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
关键词
D O I
10.1007/BF03402195
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Using the lymphocytic choriomeningitis virus (LCMV) model in mice, a number of studies show that memory cytotoxic T-lymphocyte (CTL) responses are maintained in the presence of continuous antigenic stimulation. Yet, other groups found that memory CTL specific for LCMV could last for a lifetime in mice without viral antigens. Thus, the extent to which an antigen is required for the maintenance of virus-specific CTL remains controversial. In humans, very few studies have bren conducted to investigate the relationship between the quantity of antigen and the magnitude of CTL responses. Materials and Methods: We quantified CTL precursors (CTLp) using a limiting-dilution analysis (LDA) and CTL effectors (CTLe) using a new Major Histocompatibility Complex (MHC) class I tetramer technology in six long-term nonprogressors (LTNPs) with human immunodeficiency virus type-1 (HIV-1) infection, as well as in eight patients whose viral loads were well suppressed by antiretroviral therapy. The viremia levels in these patients were measured using an reverse transcription polymerase chain reaction (RT-PCR) assay. The proviral DNA load in peripheral blood mononuclear cell (PBMC) was also measured by PCR in four LTNPs. Results: The LTNPs had high levels of HIV-1-specific memory CTLp and CTLe, while maintaining a low plasma viral load. Despite also having low viral loads, patients whose plasma viremia was well-suppressed by effective therapy had low levels of CTLe. Conclusions: Our findings suggest that a complex, rather than a monotonic, relationship exists between CTL levels and HIV-1 viremia, including what appears to be an antigenic threshold for the maintenance of CTL at a measurable level. Under conditions of "antigen excess,", CTLe levels correlate inversely with viral load. On the other hand, under conditions that are "antigen limited," the correlation appears to be direct.
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收藏
页码:803 / 809
页数:7
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