title: The shift of Th1 to Th2 immunodominance associated with the chronicity of Mycobacterium bovis bacille Calmette-Guérin infection does not affect the memory response.
abstract: In the present study we investigated the shaping and evolution of the immunodominance of the T cell response during a chronic mycobacterial infection. Using a recombinant bacille Calmette-Guérin expressing a reporter Ag, the Escherichia coli MalE protein, we analyzed the peptide specificity and the cytokine profile of the T cell response to the reporter Ag by ELISPOT. During the early steps of infection, the T cell response was focused on two dominant MalE epitopes and was characterized by a pure IFN-gamma response. Then, in the course of infection the initial IFN-gamma response to these two epitopes shifted to a mixed IFN-gamma/IL-4 response. At the same time, the peptide specificity of the T cell response was broadened to two additional MalE epitopes characterized by a unique IL-4 response resulting in the establishment of a dominant IL-4 response to the MalE protein at 16 wk postinfection. However, this phenomenon did not impair the outcome of a predominant IFN-gamma response upon subsequent MalE recall in vivo performed in the presence of CFA, a Th1-driving adjuvant. These results indicate that the Th2 nature of the immune response established during a chronic infection, which most likely reflects regulatory mechanisms to allow the return to T cell homeostasis, does not shape the Th1/Th2 nature of the memory response.
authors.affiliation: Unité de Biologie des Régulations Immunitaires and Laboratoire du BCG, Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
authors.forename: Xinan
authors.initials: X
authors.lastname: Jiao
authors.forename: Richard
authors.initials: R
authors.lastname: Lo-Man
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
authors.forename: Edith
authors.initials: E
authors.lastname: Dériaud
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000032:analysis / Q000235:genetics / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology*; D007156:Immunologic Memory; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000502:physiology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology; D033902:Periplasmic Binding Proteins / Q000008:administration & dosage / Q000032:analysis / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D029968:Escherichia coli Proteins; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; C461619:MalE protein, E coli; D010455:Peptides; D033902:Periplasmic Binding Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma