HIV-1 impairs in vitro priming of naïve T cells and gives rise to contact-dependent suppressor T cells.
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.
Che
Karlhans F
KF
Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. karlhans.fru.che@liu.se
Sabado
Rachel L
RL
Shankar
Esaki M
EM
Tjomsland
Veronica
V
Messmer
Davorka
D
Bhardwaj
Nina
N
Lifson
Jeffrey D
JD
Larsson
Marie
M
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000737:chemistry; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D002450:Cell Communication; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004220:Disulfides / Q000737:chemistry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D061026:Programmed Cell Death 1 Receptor; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D019138:Antibodies, Blocking; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004220:Disulfides; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015488:HIV Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D053221:TNF-Related Apoptosis-Inducing Ligand; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl
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