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  1. Article ; Online: Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry.

    Claireaux, Mathieu / Robinot, Rémy / Kervevan, Jérôme / Patgaonkar, Mandar / Staropoli, Isabelle / Brelot, Anne / Nouël, Alexandre / Gellenoncourt, Stacy / Tang, Xian / Héry, Mélanie / Volant, Stevenn / Perthame, Emeline / Avettand-Fenoël, Véronique / Buchrieser, Julian / Cokelaer, Thomas / Bouchier, Christiane / Ma, Laurence / Boufassa, Faroudy / Hendou, Samia /
    Libri, Valentina / Hasan, Milena / Zucman, David / de Truchis, Pierre / Schwartz, Olivier / Lambotte, Olivier / Chakrabarti, Lisa A

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 521

    Abstract: HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely ... ...

    Abstract HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control.
    MeSH term(s) CD4-Positive T-Lymphocytes/immunology ; Chemokines ; Down-Regulation ; Elite Controllers ; Gene Expression Regulation ; Gene Products, gag/metabolism ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/immunology ; Histocompatibility Antigens Class II ; Humans ; Mutation ; Receptors, CCR5/genetics ; Receptors, CCR5/metabolism ; Receptors, CXCR3 ; Virus Internalization
    Chemical Substances CCR5 protein, human ; CXCR3 protein, human ; Chemokines ; Gene Products, gag ; Histocompatibility Antigens Class II ; Receptors, CCR5 ; Receptors, CXCR3
    Language English
    Publishing date 2022-01-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-28130-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Public T cell receptors confer high-avidity CD4 responses to HIV controllers.

    Benati, Daniela / Galperin, Moran / Lambotte, Olivier / Gras, Stéphanie / Lim, Annick / Mukhopadhyay, Madhura / Nouël, Alexandre / Campbell, Kristy-Anne / Lemercier, Brigitte / Claireaux, Mathieu / Hendou, Samia / Lechat, Pierre / de Truchis, Pierre / Boufassa, Faroudy / Rossjohn, Jamie / Delfraissy, Jean-François / Arenzana-Seisdedos, Fernando / Chakrabarti, Lisa A

    The Journal of clinical investigation

    2016  Volume 126, Issue 6, Page(s) 2093–2108

    Abstract: The rare patients who are able to spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient cellular immune response. To identify the molecular determinants that underlie this response, we characterized the T ... ...

    Abstract The rare patients who are able to spontaneously control HIV replication in the absence of therapy show signs of a particularly efficient cellular immune response. To identify the molecular determinants that underlie this response, we characterized the T cell receptor (TCR) repertoire directed at Gag293, the most immunoprevalent CD4 epitope in the HIV-1 capsid. HIV controllers from the ANRS CODEX cohort showed a highly skewed TCR repertoire that was characterized by a predominance of TRAV24 and TRBV2 variable genes, shared CDR3 motifs, and a high frequency of public clonotypes. The most prevalent public clonotypes generated TCRs with affinities at the higher end of values reported for naturally occurring TCRs. The high-affinity Gag293-specific TCRs were cross-restricted by up to 5 distinct HLA-DR alleles, accounting for the expression of these TCRs in HIV controllers of diverse genetic backgrounds. Transfer of these TCRs to healthy donor CD4+ T cells conferred high antigen sensitivity and polyfunctionality, thus recapitulating key features of the controller CD4 response. Transfer of a high-affinity Gag293-specific TCR also redirected CD8+ T cells to target HIV-1 capsid via nonconventional MHC II restriction. Together, these findings indicate that TCR clonotypes with superior functions are associated with HIV control. Amplification or transfer of such clonotypes may contribute to immunotherapeutic approaches aiming at a functional HIV cure.
    MeSH term(s) Adoptive Transfer ; Adult ; Animals ; Antiretroviral Therapy, Highly Active ; CD4 Antigens/immunology ; CD4-Positive T-Lymphocytes/immunology ; Genes, T-Cell Receptor alpha ; Genes, T-Cell Receptor beta ; HIV Infections/drug therapy ; HIV Infections/genetics ; HIV Infections/immunology ; HIV Long-Term Survivors ; HIV-1 ; HLA-DR Antigens/genetics ; Humans ; Immunity, Cellular ; L Cells (Cell Line) ; Mice ; Middle Aged ; Receptors, Antigen, T-Cell/immunology ; gag Gene Products, Human Immunodeficiency Virus/immunology
    Chemical Substances CD4 Antigens ; HLA-DR Antigens ; Receptors, Antigen, T-Cell ; gag Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2016--01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI83792
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Early control of HIV-1 infection in long-term nonprogressors followed since diagnosis in the ANRS SEROCO/HEMOCO cohort.

    Madec, Yoann / Boufassa, Faroudy / Avettand-Fenoel, Veronique / Hendou, Samia / Melard, Adeline / Boucherit, Soraya / Surzyn, Janina / Meyer, Laurence / Rouzioux, Christine

    Journal of acquired immune deficiency syndromes (1999)

    2009  Volume 50, Issue 1, Page(s) 19–26

    Abstract: Background: To clarify early correlates and natural history of HIV long-term nonprogressors (LTNPs) since HIV diagnosis.: Methods: Patients enrolled in the French ANRS SEROCO/HEMOCO cohort with CD4 count >500 cells/mm3 at HIV diagnosis. LTNP status ... ...

    Abstract Background: To clarify early correlates and natural history of HIV long-term nonprogressors (LTNPs) since HIV diagnosis.
    Methods: Patients enrolled in the French ANRS SEROCO/HEMOCO cohort with CD4 count >500 cells/mm3 at HIV diagnosis. LTNP status was defined as being asymptomatic, antiretroviral free, and with CD4 cell count >500 cells/mm3 for >8 years after HIV diagnosis. In LTNPs, we modeled the biological markers' progression through a joint model. Factors associated with loss of LTNP status were identified through a Cox model.
    Results: Sixty (9%) of 664 patients were identified as LTNPs during follow-up. At enrollment, HIV RNA was <or=2.6 log copies/mL in 24% of LTNPs and HIV DNA was <or=1.85 log copies/10 peripheral blood mononuclear cells (PBMCs) in 31% vs. 3% and 8% in others. In LTNPs, HIV RNA and HIV DNA levels increased by 0.04 log copies/mL per year and 0.07 log copies/10(6) PBMCs per year during the first 8 years after diagnosis. LTNP status was lost in 36 subjects; baseline HIV DNA >1.85 log copies/10(6) PBMCs and high HIV DNA increase were associated with an increased risk of losing LTNP status [adjusted hazard ratio: 2.8 (1.2-6.8) and 2.2 (1.0-4.8), respectively].
    Conclusions: LTNP status is established in the first years of HIV infection, low HIV DNA level at enrollment and slow increase of HIV DNA being associated with maintained LTNP status.
    MeSH term(s) Adult ; Anti-HIV Agents/therapeutic use ; CD4 Lymphocyte Count ; Cohort Studies ; DNA, Viral/blood ; Disease Progression ; Female ; France/epidemiology ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; HIV-1/genetics ; Humans ; Male ; RNA, Viral/blood ; Time Factors ; Young Adult
    Chemical Substances Anti-HIV Agents ; DNA, Viral ; RNA, Viral
    Language English
    Publishing date 2009-03-18
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 645053-2
    ISSN 1944-7884 ; 1077-9450 ; 1525-4135 ; 0897-5965 ; 0894-9255
    ISSN (online) 1944-7884 ; 1077-9450
    ISSN 1525-4135 ; 0897-5965 ; 0894-9255
    DOI 10.1097/QAI.0b013e31818ce709
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2442: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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