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Background

Wacleche et al. Poster # TUPDA0101. Background.  HIV-1 infection persists in reservoirs and leads to progressive depletion of CD4+ T-cells even in subjects with slow disease progression

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Background

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  1. Wacleche et al. Poster # TUPDA0101 Background  HIV-1 infection persists in reservoirs and leads to progressive depletion of CD4+ T-cells even in subjects with slow disease progression  HIV-specific CD4+ T-cells are preferentially infected, while CMV-specific CD4+ T-cells are protected from infection in vivo  Memory CD4+ T-cells expressing the gut-homing marker CCR6 are major sites for HIV-DNA integration in vivo  Recruitment in excess of effector CD8+ T-cells in the proximity of target CD4+ T-cells is critical for the control of viral replication and disease progression Goal: to investigate the co-localization potential of HIV-specific CD8+ and CD4+ T-cells into the gut-associated lymphoid tissues (GALT) and explore the role of retinoic acid (RA) in regulating this process Methods  CFSE dilution assay was used to identify HIV- vs. CMV-specific T-cells  Polychromatic flow cytometry was used to quantify expression of the gut-homing markers integrin β7, CCR6, and CXCR3 on proliferating T-cells  ATRA and the inhibitor LE450 were used to determine the role of RA pathway in regulating expression of gut-homing molecules on HIV-specific T-cells  Studies were performed on PBMC from HIV-infected subjects with a history of slow disease progression (n=5): median CD4 counts of 670 cells/µl, median plasma viral load of 964 HIV-RNA copies/ml, and median time since infection of 15 years Wacleche et al, PLoS One 2012

  2.  Expression of the gut homing markers integrin β7, CCR6 and CXCR3 represents a « signature » for HIV-specific CD4+ T-cells p=0.0078 p=0.0019 CD4+ CD8+ NS  HIV-specific CD8+ vs CD4+ T-cells express higher, lower, and similar levels of integrin β7, CCR6, and CXCR3, respectively p=0.05 p=0.003 p=0.003 Results p=0.04 p=0.03 p=0.0007 p=0.01  ATRA upregulatesintegrinβ7 but not CCR6 expression on HIV-specific CD4+ and CD8+ T-cells CD4+ CD8+ Wacleche et al, PLoS One 2012

  3. Proposed Model Acknowledgements Authors: Vanessa Wacleche, Nicolas Chomont, Annie Gosselin, Patricia Monteiro, Mathieu Goupil, HassenKared, Cécile Tremblay, Nicole Bernard, Mohamed-RachidBoulassel, Jean-Pierre Routy, and PetronelaAncuta Financial support: CIHR, FRSQ, Fondation du CHUM, INSERM and ANRS HIV cohorts: FRSQ-SIDA Infectious Diseases Network; HIV-infected subjects Wacleche et al, PLoS One 2012

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