title: Decreased HIV-specific T-regulatory responses are associated with effective DC-vaccine induced immunity.
abstract: The role of regulatory T cells (Tregs) in vaccination has been poorly investigated. We have reported that vaccination with ex vivo-generated dendritic-cells (DC) loaded with HIV-lipopeptides (LIPO-5-DC vaccine) in HIV-infected patients was well tolerated and highly immunogenic. These responses and their relation to viral replication following analytical treatment interruption (ATI) were variable. Here, we investigated whether the presence of HIV-specific Tregs might explain these differences. Co-expression of CD25, CD134, CD39 and FoxP3 was used to delineate both antigen-specific Tregs and effectors T cells (Teffs). Median LIPO-5 specific-CD25+CD134+ polyfunctional T cells increased from 0.1% (IQR 0-0.3) before vaccination (week -4) to 2.1% (IQR 1.1-3.9) at week 16 following 4 immunizations (p=0.001) and were inversely correlated with maximum viral load following ATI (r=-0.77, p=0.001). Vaccinees who displayed lower levels of HIV-specific CD4+CD134+CD25+CD39+FoxP3+ Tregs responded better to the LIPO-5-DC vaccine. After vaccination, the frequency of HIV-specific Tregs decreased (from 69.3 at week -4 to 31.7% at week 16) and inversely correlated with HIV-specific IFN-γ-producing cells (r=-0.64, p=0.002). We show that therapeutic immunization skewed the HIV-specific response from regulatory to effector phenotype which impacts on the magnitude of viral replication following ATI.
authors: Equipe 16, Inserm U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France.
authors: Vedran
authors: V
authors: Brezar
authors: Equipe 16, Inserm U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France.
authors: Nicolas
authors: N
authors: Ruffin
authors: Vaccine Research Institute (VRI), Créteil, France; Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; CHU de Bordeaux, Pôle de santé publique, Bordeaux, France; INRIA SISTM, Talence, France.
authors: Laura
authors: L
authors: Richert
authors: Equipe 16, Inserm U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France.
authors: Mathieu
authors: M
authors: Surenaud
authors: Equipe 16, Inserm U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France.
authors: Christine
authors: C
authors: Lacabaratz
authors: Ralph M. Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, United States of America; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
authors: Karolina
authors: K
authors: Palucka
authors: Vaccine Research Institute (VRI), Créteil, France; Université Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; INSERM, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France; CHU de Bordeaux, Pôle de santé publique, Bordeaux, France; INRIA SISTM, Talence, France.
authors: Rodolphe
authors: R
authors: Thiébaut
authors: Equipe 16, Inserm U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France; Ralph M. Steinman Center for Cancer Vaccines, Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, United States of America; The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America.
authors: Jacques
authors: J
authors: Banchereau
authors: Equipe 16, Inserm U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France; Service d'immunologie clinique et maladies infectieuses, AP-HP, Hôpital H. Mondor-A. Chenevier, Créteil, France.
authors: Yves
authors: Y
authors: Levy
authors: Equipe 16, Inserm U955, Créteil, France; Faculté de médecine, Université Paris Est, Créteil, France; Vaccine Research Institute (VRI), Créteil, France.
authors: Nabila
authors: N
authors: Seddiki
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000328:Adult; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; C573415:IFNG protein, human; D007371:Interferon-gamma