Production of the HIV-Suppressive Chemokines CCL3/MIP-1α and CCL22/MDC Is Associated with More Effective Antiretroviral Therapy in HIV-Infected Children

Lambert, John S.; Machado, Elizabeth S.; Watson, Douglas C.; Sill, Anne; Lim, Jean K.; Charurat, Manhattan; Cunha, Silvia M.; Afonso, Adriana O.; Oliviera, Ricardo H.; Tanuri, Amílcar; DeVico, Anthony L.

doi:10.1097/inf.0b013e31812714db

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…At early times p.i, preservation of the Th17 subset (evaluated by different means such as plasma IL-17 levels, percentage of Th17 cells and rMFI of IL-17) correlated with lower levels of activated CD4 + T-cells, and on the other hand with both higher CD4 counts and levels of MDC/CCL22. This β chemokine has been previously associated with HIV-protective activities 15 27 , although still some controversy exist regarding its role in inhibition of HIV replication depending on the sources of the infected cells, virus strains and chemokines employed in the in vitro studies performed 28 29 30 .…”

Section: Discussionmentioning

confidence: 99%

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

Falivene

Ghiglione

Laufer

et al. 2015

Sci Rep

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The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection.

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Section: Discussionmentioning

confidence: 99%

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

Falivene

Ghiglione

Laufer

et al. 2015

Sci Rep

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“…The distribution of these chemokines varies between tissue types, and T-cell subtypes. CCL3, -4, -5, and -22 have been hypothesized to have a role in protection against HIV infection because of competitive inhibition of HIV replication and correlation with resistance or control of infection (61)(62)(63)(64)(65)(66)(67). Conversely, CCL2 is a proinflammatory chemokine that supports HIV replication and has been correlated with large viral loads and several secondary complications of HIV infection (68,69).…”

Section: The Absence Of Changes In Pd-1 Expression In Cd8mentioning

confidence: 99%

Cytokine/Chemokine Responses in Activated CD4⁺and CD8⁺T Cells Isolated from Peripheral Blood, Bone Marrow, and Axillary Lymph Nodes during Acute Simian Immunodeficiency Virus Infection

Kenway-Lynch

Das

Lackner

et al. 2014

J Virol

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Understanding the cytokine/chemokine networks in CD4؉ and CD8 ؉ T cells during the acute phase of infection is crucial to design therapies for the control of early human immunodeficiency virus ( ؉ and CD8 ؉ T cells, upregulation of ␤-chemokines, fibroblast growth factor-basic, hepatocyte growth factor, and migration inhibition factor may provide a poor prognosis. and CD8 ؉ T cells, upregulation of ␤-chemokines (CCL2 and CCL22), basic fibroblast growth factor (FGF-basic), hepatocyte growth factor (HGF), and migration inhibition factor (MIF) may provide a poor prognosis either by inducing increased virus replication or by other unknown mechanisms. Therefore, drugs targeting ␤-chemokines (CCL2 and CCL22), FGF-basic, HGF, or MIF might be important for developing effective vaccines and therapeutics against HIV. IMPORTANCE Human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection results in early depletion of CD4

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“…On the other hand, the highest plasma levels of sCD40 were found in C. Although the differences lost statistical significance after correction for multiple comparisons, a few issues are worth discussing. In previous reports, higher MDC level was associated with a better outcome in children on HAART ( Lambert et al, 2007 ) and was directly correlated with Th17 cell counts in HIV-infected subjects ( Falivene et al, 2015 ). Moreover, it had anti-HIV activity in in vitro experiments ( Pal et al, 1997 ).…”

Section: Discussionmentioning

confidence: 60%

Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates

et al. 2017

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As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC) represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC) activity were assessed in nine HIV-exposed seronegative individuals (ESN) and their corresponding HIV seropositive partners (HIV+-P), in eighteen chronically infected HIV subjects (C), nine chronically infected subjects known to be HIV transmitters (CT) and ten healthy HIV− donors (HD). Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.

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Production of the HIV-Suppressive Chemokines CCL3/MIP-1α and CCL22/MDC Is Associated with More Effective Antiretroviral Therapy in HIV-Infected Children

Cited by 8 publications

References 35 publications

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

Cytokine/Chemokine Responses in Activated CD4⁺and CD8⁺T Cells Isolated from Peripheral Blood, Bone Marrow, and Axillary Lymph Nodes during Acute Simian Immunodeficiency Virus Infection

Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates

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Production of the HIV-Suppressive Chemokines CCL3/MIP-1α and CCL22/MDC Is Associated with More Effective Antiretroviral Therapy in HIV-Infected Children

Cited by 8 publications

References 35 publications

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

Cytokine/Chemokine Responses in Activated CD4+and CD8+T Cells Isolated from Peripheral Blood, Bone Marrow, and Axillary Lymph Nodes during Acute Simian Immunodeficiency Virus Infection

Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates

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Cytokine/Chemokine Responses in Activated CD4⁺and CD8⁺T Cells Isolated from Peripheral Blood, Bone Marrow, and Axillary Lymph Nodes during Acute Simian Immunodeficiency Virus Infection