HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy

Annie Gosselin, Tomas Raul Wiche Salinas, Delphine Planas, Vanessa S. Wacleche, Yuwei Zhang, Remi Fromentin, Nicolas Chomont, Eric A. Cohen, Barbara Shacklett, Vikram Mehraj, Maged P. Ghali, Jean Pierre Routy, Petronela Ancuta

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objectives: The objective of this article is to investigate the contribution of colon and blood CD4 T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. Design: Matched sigmoid biopsies and blood samples (n13) as well as leukapheresis (n20) were collected fromchronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4 T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA), central memory (TCM; CD45RACCR7), effector (TEM/TM; CD45RACCR7), Th17 (CCR6CCR4), Th1Th17 (CCR6CXCR3), Th1 (CCR6CXCR3), and Th2 (CCR6CCR4). Methods: We used polychromatic flow cytometry for cell sorting, nested real-time PCR for HIV DNA quantification, ELISA and flow cytometry for HIV p24 quantification. HIV reactivation was induced by TCR triggering in the presence/absence of all-trans retinoic acid. Results: Compared with blood, the frequency of CCR6 TM was higher in the colon. In both colon and blood compartments, CCR6 TM were significantly enriched in HIV DNA when compared with their CCR6 counterparts (n13). In blood, integrated HIV DNA levels were significantly enriched in CCR6 versus CCR6 TCM of four of five individuals and CCR6 versus CCR6 TEM of three of five individuals. Among blood TCM, Th17 and Th1Th17 contributed the most to the pool of cells harboring integrated HIV DNA despite their reduced frequency compared with Th2, which were infected the least. HIV reactivation was induced by TCR triggering and/or retinoic acid exposure at higher levels in CCR6 versus CCR6 TM, TCM, and TEM. Conclusion: CCR6 is a marker for colon and blood CD4 T cells enriched for replication-competent HIV DNA. Novel eradication strategies should target HIV persistence in CCR6CD4 T cells from various anatomic sites.

Original languageEnglish (US)
Pages (from-to)35-48
Number of pages14
JournalAIDS
Volume31
Issue number1
DOIs
StatePublished - 2017

Fingerprint

Colon
HIV
T-Lymphocytes
DNA
Therapeutics
T-Lymphocyte Subsets
Tretinoin
Flow Cytometry
HIV Core Protein p24
Leukapheresis
Chemokine Receptors
Sigmoid Colon
Real-Time Polymerase Chain Reaction
Enzyme-Linked Immunosorbent Assay
Biopsy

Keywords

  • Antiretroviral therapy
  • CCR6
  • Central memory CD4 T cells
  • HIV reservoirs
  • Retinoic acid
  • Th17
  • Viral outgrowth assay

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Gosselin, A., Salinas, T. R. W., Planas, D., Wacleche, V. S., Zhang, Y., Fromentin, R., ... Ancuta, P. (2017). HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy. AIDS, 31(1), 35-48. https://doi.org/10.1097/QAD.0000000000001309

HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy. / Gosselin, Annie; Salinas, Tomas Raul Wiche; Planas, Delphine; Wacleche, Vanessa S.; Zhang, Yuwei; Fromentin, Remi; Chomont, Nicolas; Cohen, Eric A.; Shacklett, Barbara; Mehraj, Vikram; Ghali, Maged P.; Routy, Jean Pierre; Ancuta, Petronela.

In: AIDS, Vol. 31, No. 1, 2017, p. 35-48.

Research output: Contribution to journalArticle

Gosselin, A, Salinas, TRW, Planas, D, Wacleche, VS, Zhang, Y, Fromentin, R, Chomont, N, Cohen, EA, Shacklett, B, Mehraj, V, Ghali, MP, Routy, JP & Ancuta, P 2017, 'HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy', AIDS, vol. 31, no. 1, pp. 35-48. https://doi.org/10.1097/QAD.0000000000001309
Gosselin A, Salinas TRW, Planas D, Wacleche VS, Zhang Y, Fromentin R et al. HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy. AIDS. 2017;31(1):35-48. https://doi.org/10.1097/QAD.0000000000001309
Gosselin, Annie ; Salinas, Tomas Raul Wiche ; Planas, Delphine ; Wacleche, Vanessa S. ; Zhang, Yuwei ; Fromentin, Remi ; Chomont, Nicolas ; Cohen, Eric A. ; Shacklett, Barbara ; Mehraj, Vikram ; Ghali, Maged P. ; Routy, Jean Pierre ; Ancuta, Petronela. / HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy. In: AIDS. 2017 ; Vol. 31, No. 1. pp. 35-48.
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abstract = "Objectives: The objective of this article is to investigate the contribution of colon and blood CD4 T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. Design: Matched sigmoid biopsies and blood samples (n13) as well as leukapheresis (n20) were collected fromchronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4 T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA), central memory (TCM; CD45RACCR7), effector (TEM/TM; CD45RACCR7), Th17 (CCR6CCR4), Th1Th17 (CCR6CXCR3), Th1 (CCR6CXCR3), and Th2 (CCR6CCR4). Methods: We used polychromatic flow cytometry for cell sorting, nested real-time PCR for HIV DNA quantification, ELISA and flow cytometry for HIV p24 quantification. HIV reactivation was induced by TCR triggering in the presence/absence of all-trans retinoic acid. Results: Compared with blood, the frequency of CCR6 TM was higher in the colon. In both colon and blood compartments, CCR6 TM were significantly enriched in HIV DNA when compared with their CCR6 counterparts (n13). In blood, integrated HIV DNA levels were significantly enriched in CCR6 versus CCR6 TCM of four of five individuals and CCR6 versus CCR6 TEM of three of five individuals. Among blood TCM, Th17 and Th1Th17 contributed the most to the pool of cells harboring integrated HIV DNA despite their reduced frequency compared with Th2, which were infected the least. HIV reactivation was induced by TCR triggering and/or retinoic acid exposure at higher levels in CCR6 versus CCR6 TM, TCM, and TEM. Conclusion: CCR6 is a marker for colon and blood CD4 T cells enriched for replication-competent HIV DNA. Novel eradication strategies should target HIV persistence in CCR6CD4 T cells from various anatomic sites.",
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AU - Gosselin, Annie

AU - Salinas, Tomas Raul Wiche

AU - Planas, Delphine

AU - Wacleche, Vanessa S.

AU - Zhang, Yuwei

AU - Fromentin, Remi

AU - Chomont, Nicolas

AU - Cohen, Eric A.

AU - Shacklett, Barbara

AU - Mehraj, Vikram

AU - Ghali, Maged P.

AU - Routy, Jean Pierre

AU - Ancuta, Petronela

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N2 - Objectives: The objective of this article is to investigate the contribution of colon and blood CD4 T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. Design: Matched sigmoid biopsies and blood samples (n13) as well as leukapheresis (n20) were collected fromchronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4 T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA), central memory (TCM; CD45RACCR7), effector (TEM/TM; CD45RACCR7), Th17 (CCR6CCR4), Th1Th17 (CCR6CXCR3), Th1 (CCR6CXCR3), and Th2 (CCR6CCR4). Methods: We used polychromatic flow cytometry for cell sorting, nested real-time PCR for HIV DNA quantification, ELISA and flow cytometry for HIV p24 quantification. HIV reactivation was induced by TCR triggering in the presence/absence of all-trans retinoic acid. Results: Compared with blood, the frequency of CCR6 TM was higher in the colon. In both colon and blood compartments, CCR6 TM were significantly enriched in HIV DNA when compared with their CCR6 counterparts (n13). In blood, integrated HIV DNA levels were significantly enriched in CCR6 versus CCR6 TCM of four of five individuals and CCR6 versus CCR6 TEM of three of five individuals. Among blood TCM, Th17 and Th1Th17 contributed the most to the pool of cells harboring integrated HIV DNA despite their reduced frequency compared with Th2, which were infected the least. HIV reactivation was induced by TCR triggering and/or retinoic acid exposure at higher levels in CCR6 versus CCR6 TM, TCM, and TEM. Conclusion: CCR6 is a marker for colon and blood CD4 T cells enriched for replication-competent HIV DNA. Novel eradication strategies should target HIV persistence in CCR6CD4 T cells from various anatomic sites.

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KW - Antiretroviral therapy

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KW - HIV reservoirs

KW - Retinoic acid

KW - Th17

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