Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity
Standard
Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity. / Angin, Mathieu; Klarenbeek, Paul L; King, Melanie; Sharma, Siddhartha M; Moodley, Eshia S; Rezai, Ashley; Piechocka-Trocha, Alicja; Toth, Ildiko; Chan, Andrew T; Goulder, Philip J; Ndung'u, Thumbi; Kwon, Douglas S; Addo, Marylyn Martina.
In: PLOS ONE, Vol. 9, No. 2, 01.01.2014, p. e86920.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Regulatory T cells expanded from HIV-1-infected individuals maintain phenotype, TCR repertoire and suppressive capacity
AU - Angin, Mathieu
AU - Klarenbeek, Paul L
AU - King, Melanie
AU - Sharma, Siddhartha M
AU - Moodley, Eshia S
AU - Rezai, Ashley
AU - Piechocka-Trocha, Alicja
AU - Toth, Ildiko
AU - Chan, Andrew T
AU - Goulder, Philip J
AU - Ndung'u, Thumbi
AU - Kwon, Douglas S
AU - Addo, Marylyn Martina
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Adult
KW - Cell Proliferation
KW - Cells, Cultured
KW - Cytotoxicity, Immunologic
KW - DNA Methylation
KW - Female
KW - Flow Cytometry
KW - Forkhead Transcription Factors
KW - Gastrointestinal Tract
KW - Gene Expression
KW - HIV Infections
KW - HIV-1
KW - High-Throughput Nucleotide Sequencing
KW - Host-Pathogen Interactions
KW - Humans
KW - Immunophenotyping
KW - Infant
KW - Lymphoid Tissue
KW - Male
KW - Middle Aged
KW - Receptors, Antigen, T-Cell
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - T-Lymphocytes, Regulatory
U2 - 10.1371/journal.pone.0086920
DO - 10.1371/journal.pone.0086920
M3 - SCORING: Journal article
C2 - 24498287
VL - 9
SP - e86920
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 2
ER -
