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PLoS One. 2014 Feb 3;9(2):e86920. doi: 10.1371/journal.pone.0086920. eCollection 2014.

Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity.

Author information

1
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America.
2
Department of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.
3
HIV Pathogenesis Programme, Doris Duke Medical Research Institute and KwaZulu-Natal Research Institute for TB and HIV, University of KwaZulu-Natal, Durban, South Africa.
4
Massachusetts General Hospital, Gastrointestinal Unit, Boston, Massachusetts, United States of America.
5
HIV Pathogenesis Programme, Doris Duke Medical Research Institute and KwaZulu-Natal Research Institute for TB and HIV, University of KwaZulu-Natal, Durban, South Africa ; Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
6
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute and KwaZulu-Natal Research Institute for TB and HIV, University of KwaZulu-Natal, Durban, South Africa.
7
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America ; Massachusetts General Hospital, Division of Infectious Diseases, Boston, Massachusetts, United States of America.
8
Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America ; Massachusetts General Hospital, Division of Infectious Diseases, Boston, Massachusetts, United States of America ; Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+) Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by deep sequencing. Flow-based T-cell proliferation and chromium release cytotoxicity assays were used to determine Treg suppressive function. Tregs from HIV-1 positive individuals, including infants, were successfully expanded from PBMC and GALT. Expanded Tregs expressed high levels of FOXP3, CTLA4, CD39 and HELIOS and exhibited a highly demethylated TSDR (Treg-specific demethylated region), characteristic of Treg lineage. The TCRß repertoire was maintained following Treg expansion and expanded Tregs remained highly suppressive in vitro. Our data demonstrate that Tregs can be expanded from blood and tissue compartments of HIV-1+ donors with preservation of Treg phenotype, function and TCR repertoire. These results are highly relevant for the investigation of potential future therapeutic use, as currently investigated for other disease states and hold great promise for detailed studies on the role of Tregs in HIV-1 infection.

PMID:
24498287
PMCID:
PMC3911933
DOI:
10.1371/journal.pone.0086920
[Indexed for MEDLINE]
Free PMC Article

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