title: Influence of pathological progression on the balance between cellular and humoral immune responses in bovine tuberculosis.
abstract: Studies of tuberculosis have suggested a shift in dominance from a T helper type 1 (Th1) towards a Th2 immune response that is associated with suppressed cell-mediated immune (CMI) responses and increased humoral responses as the disease progresses. In this study a natural host disease model was used to investigate the balance of the evolving immune response towards Mycobacterium bovis infection in cattle with respect to pathogenesis. Cytokine analysis of CD4 T-cell clones derived from M. bovis-infected animals gave some indication that there was a possible relationship between enhanced pathogenesis and an increased ratio of Th0 [interleukin-4-positive/interferon-gamma-positive (IL-4(+)/IFN-gamma(+))] clones to Th1 (IFN-gamma(+)) clones. All animals developed strong antimycobacterial CMI responses, but depressed cellular responses were evident as the disease progressed, with the IFN-gamma test failing to give consistently positive results in the latter stages. Furthermore, a stronger Th0 immune bias, depressed in vitro CMI responses, elevated levels of IL-10 expression and enhanced humoral responses were also associated with increased pathology. In minimal disease, however, a strong Th1 immune bias was maintained and an anti-M. bovis humoral response failed to develop. It was also seen that the level of the anti-M. bovis immunoglobulin G1 (IgG1) isotype antibody responses correlated with the pathology scores, whereas CMI responses did not have as strong a relationship with the development of pathology. Therefore, the development and maintenance of a Th1 IFN-gamma response is associated with a greater control of M. bovis infection. Animals progressing from a Th1-biased to a Th0-biased immune response developed more extensive pathology and performed less well in CMI-based diagnostic tests but developed strong IgG1 humoral responses.
authors.affiliation: Veterinary Sciences Division, The Department of Agriculture and Rural Development, Stoney Road, Stormont, Belfast, BT4 3SD, UK. michael.welsh@dardni.gov.uk
authors.forename: Michael D
authors.initials: MD
authors.lastname: Welsh
authors.forename: Rodat T
authors.initials: RT
authors.lastname: Cunningham
authors.forename: David M
authors.initials: DM
authors.lastname: Corbett
authors.forename: R Martyn
authors.initials: RM
authors.lastname: Girvin
authors.forename: James
authors.initials: J
authors.lastname: McNair
authors.forename: Robin A
authors.initials: RA
authors.lastname: Skuce
authors.forename: David G
authors.initials: DG
authors.lastname: Bryson
authors.forename: John M
authors.initials: JM
authors.lastname: Pollock
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002417:Cattle; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D014380:Tuberculosis, Bovine / Q000276:immunology* / Q000473:pathology*
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D014373:Tuberculin; D007371:Interferon-gamma