Abstract
Priming of T cells in lymphoid tissues of HIV-infected individuals occurs in the presence of HIV-1. DC in this milieu activate T cells and disseminate HIV-1 to newly activated T cells, the outcome of which may have serious implications in the development of optimal antiviral responses. We investigated the effects of HIV-1 on DC-naïve T-cell interactions using an allogeneic in vitro system. Our data demonstrate a dramatic decrease in the primary expansion of naïve T cells when cultured with HIV-1-exposed DC. CD4(+) and CD8(+) T cells showed enhanced expression of PD-1 and TRAIL, whereas CTLA-4 expression was observed on CD4(+) T cells. It is worth noting that T cells primed in the presence of HIV-1 suppressed priming of other naïve T cells in a contact-dependent manner. We identified PD-1, CTLA-4, and TRAIL pathways as responsible for this suppresion, as blocking these negative molecules restored T-cell proliferation to a higher degree. In conclusion, the presence of HIV-1 during DC priming produced cells with inhibitory effects on T-cell activation and proliferation, i.e. suppressor T cells, a mechanism that could contribute to the enhancement of HIV-1 pathogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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2,2'-Dipyridyl / analogs & derivatives
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2,2'-Dipyridyl / chemistry
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Antibodies, Blocking / pharmacology
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / immunology
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Apoptosis Regulatory Proteins / metabolism
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CTLA-4 Antigen
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Cell Communication
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Cell Proliferation / drug effects
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Cells, Cultured
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / pathology
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Dendritic Cells / virology
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Disulfides / chemistry
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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HIV Antigens / immunology
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HIV Antigens / metabolism
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HIV Infections / immunology*
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HIV-1 / chemistry
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HIV-1 / immunology*
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HIV-1 / pathogenicity
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Humans
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Lymphocyte Activation / drug effects
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Programmed Cell Death 1 Receptor
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Signal Transduction
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
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T-Lymphocyte Subsets / virology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / pathology
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T-Lymphocytes, Regulatory / virology
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TNF-Related Apoptosis-Inducing Ligand / genetics
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TNF-Related Apoptosis-Inducing Ligand / immunology
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TNF-Related Apoptosis-Inducing Ligand / metabolism
Substances
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Antibodies, Blocking
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Antigens, CD
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Apoptosis Regulatory Proteins
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CTLA-4 Antigen
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CTLA4 protein, human
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Disulfides
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FOXP3 protein, human
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Forkhead Transcription Factors
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HIV Antigens
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
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TNF-Related Apoptosis-Inducing Ligand
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2,2'-dipyridyl disulfide
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2,2'-Dipyridyl