title: Impaired M. tuberculosis Antigen-Specific IFN-γ Response without IL-17 Enhancement in Patients with Severe Cavitary Pulmonary Tuberculosis.
abstract: BACKGROUND
  Th1 cells play an essential role in immune protection against tuberculosis. Th17 cells might be involved with immune pathology in active human tuberculosis (TB). The balance between Th1 and Th17 cells in patients with cavitary tuberculosis needs to be clarified which might help understanding the immunological basis of pathologic pathogenesis in TB.
  
  
  METHODS
  Initially treated pulmonary TB (PTB) patients with or without cavities were recruited before chemotherapy. We isolated peripheral blood mononuclear cells, stimulated with phytohemagglutinin (PHA), PPD, or ESAT-6 antigens, and assayed supernatant IFN-γ and IL-17 by ELISA after 24 or 72 hours incubation, respectively. Cells were also stained with antibodies to CD3, CD4, CD8, IFN-γ or IL-17 and the proportion of stained cells was measured by flow cytometry.
  
  
  RESULTS
  We found wide variation of IFN-γ response in active PTB patients, but less subject-to-subject variation of IL-17 was observed as we previously reported. There were no significant differences in IFN-γ and IL-17 between cavitary and non-cavitary PTB; however, we found decreased IFN-γ secretion in severe cavitary PTB compared to mild lesion non-cavitary PTB (p < 0.05). We also found a decrease in the proportion of CD3+CD4+ T cells in the blood of severe cavitary PTB patients (p < 0.05).
  
  
  CONCLUSIONS
  IL-17 seemed to have no association with the formation of cavities in active PTB from the study of PBMC. Impaired IFN-γ without IL-17 enhancement occurs in peripheral blood during severe cavitary PTB. Our results demonstrate that M. tuberculosis antigen-specific Th1 response is decreased when PTB lesions develop to severe cavities.
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
authors.forename: Heping
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Mai
authors.affiliation: Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Su
authors.affiliation: Division of Infectious Diseases, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Ernst
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000378:metabolism / Q000628:therapy
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D020381:Interleukin-17; D007371:Interferon-gamma