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Le Touquet – Paris-Plage, France

Xie J.,French Institute of Health and Medical Research | Lu W.,French Institute of Health and Medical Research | Samri A.,French Institute of Health and Medical Research | Samri A.,Laboratoire DImmunite et Infections | And 13 more authors.
AIDS | Year: 2010

Objectives: A superior capacity of controlling HIV has been attributed to CD8+ T cells directed against HIV-Gag compared to Nef, particularly in the context of some protective human leukocyte antigen (HLA) alleles. To further elucidate this protective effect, we compared the multifunctional and differentiation characteristics of CD8+ T cells specific for HIV-Gag and Nef in HLA-B57/5801-positive and negative nonprogressors. Methods: A head-to-head comparison of CD8+ T cells specific for HIV-Gag and Nef frequencies, cytokine production and differentiation was conducted, in 11 HLA-B57/5801 and 11 HLA-B57/5801 HIV-infected individuals selected from a cohort of 53 nonprogressors by using IFN-γ-ELISpot assay and flow cytometry analysis of intracellular cytokine production and differentiation profile. Correlations with HIV parameters were studied. Results: Frequencies of Gag-specific but not of Nef-specific CD8+ T cells correlated with peripheral blood mononuclear cell (PBMC)-associated HIV-DNA. The HIV-Gag and Nef-specific CD8+ T cells did not differ for IL-2 production in either HLA-B57/5801 or HLA-B57/5801 individuals. The IFN-γ-producing Gag-specific CD8+ T cells in HLA-B57/5801 individuals significantly differed from their Nef-specific counterparts by displaying higher proportions of central memory CD4+5RACCR7 cells positive for CD27+. This differentiation pattern was not observed in HLA-B57/5801 individuals. Only these HLA-B57/5801-positive Gag-specific CD27+ central memory CD8+ T cells, but not their Nef-specific counterparts, negatively correlated with cell-associated HIV-DNA. Conclusion: HLA-B57/5801 drives a preferential CD27+ differentiation of central memory CD8+ T cells directed against HIV-Gag but not Nef that may contribute to the ability of Gag-specific CD8+ T cells to better control HIV in HLA-B57/5801 nonprogressors. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Billot K.,University Pierre and Marie Curie | Parizot C.,Laboratoire dImmunologie Cellulaire et Tissulaire | Arrouss I.,University Pierre and Marie Curie | Mazier D.,University Pierre and Marie Curie | And 3 more authors.
Leukemia Research | Year: 2010

The Aiolos transcription factor plays a crucial role in the control of lymphocyte differentiation and proliferation. The expression of Aiolos isoform has been studied in lymphoid pathologies but nothing is known about its expression in unaffected human hematopoietic subpopulations. In this manuscript we show for the first time the differential Aiolos expression at the RNA and protein level in hematopoietic cell subpopulations. B cells express higher levels of Aiolos than NK and T cells while monocytes express almost undetectable levels of Aiolos. Moreover, human CD34 (+) progenitors do not express Aiolos. We did not observe significant difference when comparing naive to memory T and B cells, but we observed an important difference between Bright and Dim NK cells. Furthermore, we show that, in addition to hematopoietic cells, non hematopoietic cell lines such as MCF-7, SW480, HEK, PC3 and HeLa also express Aiolos. © 2009 Elsevier Ltd. Source

Ladell K.,University of Cardiff | Hashimoto M.,Kumamoto University | Iglesias M.C.,University Pierre and Marie Curie | Wilmann P.G.,Monash University | And 23 more authors.
Immunity | Year: 2013

The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8+ T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK263-272) presented by human leukocyte antigen (HLA)-B*2705. We found that cross-reactive CD8+ T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B*2705+ individuals. A protective CD8+ T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation. © 2013 Elsevier Inc. Source

Goulenok T.,University Pierre and Marie Curie | Boyd A.,French Institute of Health and Medical Research | Larsen M.,University Pierre and Marie Curie | Fastenackels S.,University Pierre and Marie Curie | And 13 more authors.
AIDS | Year: 2015

Objectives: Increased risk of cardiovascular disease in patients infected with HIV has been attributed to immune activation, inflammation, and immunosenescence, all of which are linked to chronic immune activation by viral infections, particularly cytomegalovirus (CMV). Our aim is to evaluate the impact of these atherogenic markers in HIV-infected patients who never smoked. Design: Exposure-matched, cross-sectional study. Methods: In 59 HIV-infected individuals [n=30 undergoing >4 years of antiretroviral therapy (ART); n=29 never treated with ART] and 30 age-matched HIV-negative controls, we measured the level of activation and senescence, as well as the frequency of CMV-specific T cells, on peripheral blood mononuclear cells, while examining their association with carotid intima-media thickness. Partial correlations were adjusted for age, systolic blood pressure, and nadir CD4 cell count. Results: The previously described roles of T-cell activation, CMV, and immunosenescence in the atherosclerotic risk of HIV-infected patients, as assessed by carotid intima- media thickness, were not apparent in our cohort of particularly 'healthy' HIV-infected never-smokers. Conclusion: In HIV-infected individuals at low cardiovascular disease risk, our data show that the increased risk of carotid atherosclerosis is not associated with immunological markers described to be associated with HIV disease progression. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Source

Sauce D.,French Institute of Health and Medical Research | Larsen M.,University Pierre and Marie Curie | Larsen M.,Laboratoire dImmunologie Cellulaire et Tissulaire | Fastenackels S.,French Institute of Health and Medical Research | And 28 more authors.
Blood | Year: 2011

The mechanisms of CD4+ T-cell count decline, the hallmark of HIV disease progression, and its relationship to elevated levels of immune activation are not fully understood. Massive depletion of CD4+ T cells occurs during the course of HIV-1 infection, so that maintenance of adequate CD4+ T-cell levels probably depends primarily on the capacity to renew depleted lymphocytes, that is, the lymphopoiesis. We performed here a comprehensive study of quantitative and qualitative attributes of CD34+ hematopoietic progenitor cells directly from the blood of a large set of HIV-infected persons compared with uninfected donors, in particular the elderly. Our analyses underline a marked impairment of primary immune resources with the failure to maintain adequate lymphocyte counts. Systemic immune activation emerges as a major correlate of altered lymphopoiesis, which can be partially reversed with prolonged antiretroviral therapy. Importantly, HIV disease progression despite elite control of HIV replication or virologic success on antiretroviral treatment is associated with persistent damage to the lymphopoietic system or exhaustion of lymphopoiesis. These findings highlight the importance of primary hematopoietic resources in HIV pathogenesis and the response to antiretroviral treatments. © 2011 by The American Society of Hematology. Source

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