title: Decreased frequencies of circulating CD4⁺ T follicular helper cells associated with diminished plasma IL-21 in active pulmonary tuberculosis.
abstract: BACKGROUND
  Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.
  To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.
  
  
  RESULTS
  We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.
  
  
  CONCLUSIONS
  Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Nathella Pavan
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: Government Stanley Medical Hospital, Chennai, India.
authors.forename: Rathinam
authors.initials: R
authors.lastname: Sridhar
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Luke E
authors.initials: LE
authors.lastname: Hanna
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Vaithilingam V
authors.initials: VV
authors.lastname: Banurekha
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India; Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein / Q000378:metabolism; D016753:Interleukin-10; D007378:Interleukins / Q000097:blood*; D055985:Latent Tuberculosis / Q000097:blood / Q000276:immunology; D018655:Lymphocyte Count; D010950:Plasma Cells / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D000942:Antigens, Bacterial; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556692:ICOS protein, human; C508609:IL10 protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000098546:Interleukin-21