Decreased Frequencies of Circulating CD4+ T Follicular Helper Cells Associated with Diminished Plasma IL-21 in Active Pulmonary Tuberculosis |
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| Authors: | Nathella Pavan Kumar Rathinam Sridhar Luke E. Hanna Vaithilingam V. Banurekha Thomas B. Nutman Subash Babu |
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| Affiliation: | 1. National Institutes of Health–International Center for Excellence in Research, Chennai, India.; 2. National Institute for Research in Tuberculosis, Chennai, India.; 3. Government Stanley Medical Hospital, Chennai, India.; 4. Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.; University Medical Center Freiburg, Germany, |
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| Abstract: | BackgroundCirculating 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.Aims/MethodologyTo determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells exvivo 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.ResultsWe found that both exvivo 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 invitro.ConclusionsThus, PTB is characterized by adiminution in the frequency of Tfh cell subsets. |
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