IL-10-secreting T cells from HIV-infected pregnant women downregulate HIV-1 replication: effect enhanced by antiretroviral treatment

Bento, Cleonice A.M.; Hygino, Joana; Andrade, Regis M.; Saramago, Carmen S.M.; Silva, Renato G; Silva, Agostinho A.L.; Linhares, Ulisses C.; Brindeiro, Rodrigo de Moraes; Tanuri, Amílcar; Rosenzwajg, Michèlle; Klatzmann, David; Andrade, Arnaldo F.B.

doi:10.1097/qad.0b013e328317461e

Cited by 31 publications

(22 citation statements)

References 46 publications

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“…Proinflammatory cytokines such as TNF-α trigger nuclear translocation of NF-κB, which is critical for the initiation of HIV LTR transcription (38, 67). In contrast, the immunosuppressive cytokine IL-10 negatively regulates HIV replication by interfering with CCR5 and CXCR4 expression and cell responsiveness to TCR triggering (33–36). The present study demonstrated that IFN-γ, IL-10, TNF-α, IL-2, CCL3, and CCL5 were mainly produced by CXCR3 + CCR6 + and CXCR3 + CCR6 − T cells, whereas CCR4 + CCR6 + and CCR4 + CCR6 − T cells were sources of IL-17 and IL-5, respectively (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

Gosselin

Monteiro

Chomont

et al. 2009

The Journal of Immunology

285

412

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There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 and CXCR4 and were permissive to R5 and X4 HIV replication. CCR4+CCR6− T cells expressed CXCR4 but not CCR5 and were permissive to X4 HIV only. CXCR3+CCR6− T cells expressed CCR5 and CXCR4 but were relatively resistant to R5 and X4 HIV in vitro. Total CCR6+ T cells compared with CCR6− T cells harbored higher levels of integrated HIV DNA in treatment-naive HIV-infected subjects. The frequency of total CCR6+ T cells and those of CCR4+CCR6+ and CXCR3+CCR6+ T cells were diminished in chronically infected HIV-positive subjects, despite viral-suppressive therapy. A high-throughput analysis of cytokine profiles identified CXCR3+CCR6+ T cells as a major source of TNF-α and CCL20 and demonstrated a decreased TNF-α/IL-10 ratio in CXCR3+CCR6− T cells. Finally, CCR4+CCR6+ and CXCR3+CCR6+ T cells exhibited gut- and lymph node-homing potential. Thus, we identified CCR4+CCR6+ and CXCR3+CCR6+ T cells as highly permissive to HIV replication, with potential to infiltrate and recruit more CCR6+ T cells into anatomic sites of viral replication. It is necessary that new therapeutic strategies against HIV interfere with viral replication/persistence in discrete CCR6+ T cell subsets.

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Section: Discussionmentioning

confidence: 99%

Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

Gosselin

Monteiro

Chomont

et al. 2009

The Journal of Immunology

285

412

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“…Although the administration of IL-10 to chronically HIV-infected subjects results in little or no impact on viral replication [28], inhibition of HIV replication by IL-10 has been clearly demonstrated in vitro [29]. Furthermore, high IL-10 plasma levels have been associated with the control of viral replication during pregnancy [30]. Altogether, these studies suggest that IL-10 may contribute to viral persistence, although the potential role of IL-10 on the establishment of the latent viral reservoir has not been formally demonstrated yet.…”

Section: Role Of Cytokines In the Establishment Of The Latent Viramentioning

confidence: 99%

The role of cytokines in the establishment, persistence and eradication of the HIV reservoir

Vandergeeten

Fromentin

Chomont

2012

Cytokine & Growth Factor Reviews

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“…Third, increased renal blood flow during pregnancy [26] may enhance the clearance of some renally excreted drugs such as most of the NRTIs. Recently, IL-10 plasma concentrations were associated with the control of HIV viral load in pregnant women, the reduction of the risk of vertical transmission [27,28]. All these factors can justify the lack of additional virological failure in women with substandard antiretroviral concentrations during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Antiretroviral Therapeutic Drug Monitoring in HIV-Infected Pregnant Women: Maternal Immunovirological Outcome at Delivery and During the 18 Month Follow-Up Period

Nicastri

Ivanović

Signore

et al. 2012

CHR

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No data are available on the long-term immunovirological outcome of HIV-positive pregnant women experiencing sub-therapeutic antiretroviral drug (ARV) concentrations during pregnancy. The objective of our study was to assess the long-term virological outcome in pregnant women treated with HAART. A prospective, multi-center study enrolled 60 HIV-infected pregnant women stratified into 3 groups according to the response to HAART. Group A, women successfully treated with HAART; Group B, women with confirmed virological failure during HAART; Group C, women successfully treated with HAART during pregnancy for prevention of vertical transmission only. Smoking, alcohol use, low adherence to therapy, and increased viral load at delivery were significantly associated to virological failure at univariate analysis. At multivariate regression analysis, only adherence to therapy was reported as an independent variable related to the virological response (p < 0.001). Virological failure during follow-up was reported in 2 (25.0%) of the 8 women with sub therapeutic Ctrough and in 4 of the 33 (12.1%) women with therapeutic Ctrough (p=0.33). In group C, the viro-immunological set points during follow-up did not differ from those observed before HAART initiation. No significantly increased rate of virological failure after delivery was reported in women with sub-therapeutic ARV concentrations during pregnancy and long-term follow-up. The long-term virological outcome was independently associated to reduced adherence to therapy. Evaluation of the clinical impact of the low plasma ARV concentrations during pregnancy on the long-term virological outcome deserves further larger studies.

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IL-10-secreting T cells from HIV-infected pregnant women downregulate HIV-1 replication: effect enhanced by antiretroviral treatment

Cited by 31 publications

References 46 publications

Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

The role of cytokines in the establishment, persistence and eradication of the HIV reservoir

Antiretroviral Therapeutic Drug Monitoring in HIV-Infected Pregnant Women: Maternal Immunovirological Outcome at Delivery and During the 18 Month Follow-Up Period

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