CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

women (19.78% ± 7.64 vs 54.29 % ± 10.05; p=0.02). Interestingly, in the HIV infected women the ratio of alpha beta to gamma delta T cells was significantly increased compared to HIV negative women (3.16 ± 1.45 vs 0.42 ± 0.17, p=0.04). Conclusions: Current knowledge of the immune dynamics at the female reproductive tract is limited at best. We report for the first time, the unique GD1 T cells are a predominant T cell subset within cervical mononuclear cells. By eliminating cervical GD1, HIV cripples an important antiviral effector subset and removes a normal control over inflammation resulting in HIV persistence and progressing disease. We propose that evaluation of GD T cell responses could be used as a novel marker of mucosal vulnerability in women with HIV infection or at risk for HIV. Funded by WHIS (U01 AI103397) and Miami CFAR ( P30AI073961). 274 T Regulatory Cells Disrupt the CCL20-CCR6 Axis Driving Th17 Homing to the Gut Claire Loiseau 1 ; Mary Requena 1 ; Michelle Cazabat 1 ; Nicolas Carrere 2 ; Bertrand Suc 2 ; Bruno Marchou 2 ; Jacques Izopet 1 ; Pierre Delobel 1 1 Inserm, Toulouse, France; 2 Centre Hospitalier Universitaire de Toulouse, Toulouse, France Background: During HIV-1 infection, the integrity of the intestinal immune barrier is disrupted due to a deep depletion of CD4 + T cells in the gut, including Th17 cells, a T cell subset exerting a major role in antimicrobial immunity. The translocation of microbial products from the gut lumen into the bloodstream, associated with Th17 cells loss, has been linked with systemic inflammation. Despite effective cART, CD4 + T cells in the lamina propria are incompletely restored in most individuals. The CCL20-CCR6 axis drives Th17 cells trafficking to the gut. We thus assess the factors regulating the expression of CCL20 by the enterocytes, and notably the role of the cytokines produced by Treg and Th17 cells. Methods: Small bowell biopsies were obtained by endoscopy in 20 HIV-infected individuals. All of them had prolonged suppression of HIV-1 RNA in the plasma <50 copies/ mL under cART for about 5 years. Their median level of blood CD4 + T cells was of 668 cells/ m L. Ten healthy HIV-1-negative individuals were used as controls. CCL20 mRNA was quantified by qRT-PCR. To explore the factors regulating CCL20 expression by the enteroyctes, we developped an ex-vivo system of human primary enterocytes (obtained from small bowel surgical resections of HIV-negative individuals) cultured as a tight monolayer on transwells. The effect of IL-17, IL-10, and TGF- β 1 on CCL20 expression was assessed. A coculture was done between the enterocytes and various proportions of Th17/Treg cells, sorted from PBMCs on the basis of their CD4 + CXCR3 - CCR6 + and CD4 + CD127 low CD49d - phenotype respectively (StemCell), and activated by PMA/ionomycin. The expression of CCL20 by the enterocytes was evaluated by qRT-PCR and ELISA. Results: In small bowell biopsies of HIV-infected individuals receiving effective cART, CCL20 mRNA was significantly reduced compared to healthy controls ( P <0.05). Ex-vivo on human primary enterocytes, IL-17A increases CCL20 expression whereas both IL-10 and TGF- β 1 reduce it. In coculture expriments, CCL20 expression decreases as the Th17/Treg ratio skews from Th17 to Treg cells (Figure 1).

Poster Abstracts

Conclusions: The CCL20-CCR6 axis driving Th17 cells gut homing is altered in HIV-infected individuals despite effective cART. A persistently imbalanced Th17/Treg ratio in the lamina proria could contribute to the reduced production of CCL20 by the enterocytes despite an effective cART. A vicious circle could arise between low CCL20 expression and the defective gut-homing of CD4 + T cells, notably Th17 cells.

WEDNESDAY, FEBRUARY 25, 2015 Session P-C3 Poster Session

Poster Hall

2:30 pm– 4:00 pm Innate and Unconventional T-Cell Responses 275 Effect of KIR2D-Mediated Immunity on Clinical Outcome Among CRF01_AE-Infected Thais

Masahiko Mori 1 ; NuanjunWichukchinda 2 ; Reiko Miyahara 1 ; Archawin Rojanawiwat 2 ; Panita Pathipvanich 3 ;Toshiyuki Miura 1 ; MichioYasunami 1 ; Koya Ariyoshi 1 ; Pathom Sawanpanyalert 2 1 Institute of Tropical Medicine, Nagasaki University, Nagasaki City, Japan; 2 Ministry of Public Health, Nonthaburi, Thailand; 3 Day Care Centre, Lampang Hospital, Lampang, Thailand Background: Class I human leukocyte antigen (HLA) molecule contributes to the immune control of HIV through antigen presentation to both cytotoxic T lymphocytes (CTL) and natural killer cells (NK). CTL contribution to HIV control through antigen presentation by protective HLA alleles, such as HLA-B*57 and HLA-B*27, has been studied well previously. However, reports on the NK cell contribution, with the exception of the protective effect of HLA-Bw4 and its ligand killer immunoglobulin-like receptor (KIR) 3DL1 and 3DS1 in HIV disease, are limited. In particular, studies about HLA-C-KIR2D on HIV control remain sparse. Methods: 209 HIV-1 CRF01_AE-infected treatment-naïve Thais were recruited, and the effects of HLA-C-KIR2D on clinical outcome were statistically analyzed. Results: 1) HLA-B*46:01, which worked as an HLA-C1 allele binding the same type of ligands despite being an HLA-B allele, was identified as the most predominant HLA-B allele (29% in the population frequency). 2) In the analysis of the viral set point difference among HLA-C1-positive individuals, subjects with KIR2DL3 had significantly higher set point compared to the subjects without KIR2DL3 (median 4.8 vs 4.2 log copies/ml, p=0.033 by Mann-Whitney U-test). 3) In multivariate analysis, the number of HLA-C1-KIR2DL3 associations (ranging from subjects having no HLA-C1-KIR2DL3 associations to subjects having up to four combinations; the KIR2DL3-positive individuals with HLA-B*46:01

235

CROI 2015