|Director : Rivière Yves (email@example.com)|
Cell mediated immune responses are a major determinant in the pathogenesis of viral infections. The functions of antigen specific T lymphocytes are required for recovery from viral infections, for clearance of virus or control of persistent infection. On the other hand, an antiviral immune response may also result in immunopathology when an inflammatory response destroys cells infected by a relatively non cytopathic virus. The major goal of our group is to study -in vitro and in vivo-the role of viral-specific cytotoxic responses (CTL) in two human viral infections, Human Immunodeficiency Virus type1 (HIV-1), and Hepatitis C virus (HCV).
A. CTL and Pediatric infection : Not all tetramer binding CD8+ T cells can produce cytokines and chemokines involved in the effector functions of virus-specific CD8+ T lymphocytes in HIV-1 infected children. F. Buseyne, E.Montchatre, N. Bellal,, coll with :D.Scott-Algara, Institut Pasteur; S.Blanche, C.Rouzioux ,CHU Necker-Enfants Malades; J LeChenadec, J Warszawski ,INSERM CHU Bicêtre.
B. Exogenous presentation of HIV particles to CD8+ lymphocytes: role of non-replicative HIV particules in the induction of primary HIV-specific CD8+ T lymphocytes. F.Buseyne, C.Retiere, M.Nowakowski coll. with A. Morris,O.Schwartz (Institut Pasteur) et J.P Abastado (IDM, Paris)
C. Control of viral replication by CD8+ T lymphocytes, M. Février, coll with A. Talarmin, Institut Pasteur de Guyane.
D. Animal model: DNA based immunisation in macaque. Collaborative studies. with AL Puaux et ML. Michel (INSERMU163, et Institut Pasteur) ,R.Legrand (CEA, Fontenay) et AM Aubertin,(INSERM, Strasbourg).
Recent efforts to design an HIV-1 vaccine candidate have focused on means of eliciting antiviral T-cell responses. We tried to improve the immunogenicity of DNA vaccines by designing hybrid DNA constructs encoding hepatitis B surface antigen fused to antigenic domains of simian/human immunodeficiency virus (SHIV 89.6P). Immunisation with hybrid DNA induced both effector and long-lasting precursor T cells. Following boosting with a recombinant modified vaccinia Ankara (rMVA) producing full-length SIV and HIV antigens, it appeared that priming with hybrid DNA had increased virus-specific T-cell responses in terms of both the number of virus-specific IFN-γ-secreting T cells and virus-specific lymphoproliferation. After intrarectal challenge with SHIV 89.6P, immunised animals demonstrated early control of SHIV 89.6P replication and stable CD4+ T cell counts (Puaux et al, 2004).
E Role of HCV-specific T cell responses in HCV-exposed uninfected infected individuals. G. Janvier coll with S.Pol, Hepatology, JL. Bresson,CIC, ML Chaix, Virology, CHU Necker-Enfants-Malades.
Hepatitis C virus (HCV) specific cytotoxic T lymphocytes have been detected in the peripheral blood and the liver of patients with chronic HCV-infection. In most cases, these activities have been evidenced after multiple cycles of virus-specific stimulation in vitro. A beneficial role of HCV-specific T cell responses has been proposed during acute HCV infection: a vigorous T cell response has been evidenced in subjects with spontaneous recovery of infection. In addition, in experimentally infected chimpanzees, intrahepatic CD8 T-cell responses directed to multiple regions of HCV were correlated with the recovery of HCV infection. Our goal was to study the role of virus-specific T cell responses in exposed uninfected individuals (stable partners of HCV-chronically infected subjects) which may explain the protection from infection despite the absence of detection of HCV specific antibodies, and to identifiy virus-specific T-cell epitopes involved in protection. Characterization of HCV-core specific responses was performed from fresh and in vitro stimulated PBMC from 20 exposed uninfected individuals and their 20 HCV-infected spouses and 20 unexposed uninfected volunteers. The specificity of virus-specific T cell responses was studied by γ-interferon Elispot assays using a panel of fifteen-mer peptides overlapping by 10 residues and covering the entire core sequence. When memory Tcell were expanded after in vitro stimulation, the frequency of responders was higher in chronic carrier and in exposed uninfected compared to the non exposed uninfected control group. Both the N-terminal and the central regions were the main targets for the chronic HCV carrier and or exposed uninfected groups while in the control group the target of the T cell responses was the central region.The results suggest a protective role of viral specific T cell activities in exposed uninfected spouses of HCV-infected patients. The identification of HCV epitopes in a such protection might be of importance for vaccine development.
Keywords: HCV, CTL, HIV, Infant, Immune reconstitution, Antigen presentation
|Publications 2004 of the unit on Pasteur's references database|
|Office staff||Researchers||Scientific trainees||Other personnel|
|Evelyne TALPIN (firstname.lastname@example.org)
||BUSEYNE Florence, IP (email@example.com)
FEVRIER Michèle, CNRS (firstname.lastname@example.org)
RIVIERE Yves , IP (email@example.com)
|AUCHER Anne Stagiaire DEA (firstname.lastname@example.org)
BELLAL Nassima médecin stagiaire
DECALF Jérémie stagiaire DEA (email@example.com)
JOLY Etienne , stagiaire CR INSERM
RETIERE Christelle, stagiaire post doctoral (firstname.lastname@example.org)
|COQUELIN Anne Sophie stagiaire ESTBA (email@example.com)
JANVIER Geneviève, technicienne (firstname.lastname@example.org)
MONCHATRE Elisabeth, technicienne (email@example.com)
NOWAKOWSKI Mireille, technicienne (firstname.lastname@example.org)
ROCHAS Caroline stagiaire ESTBA (email@example.com)