Abstract

In the current study of Mycobacterium tuberculosis (MTB)-specific T and B cells, we found that MTB-specific peptides from early secreted antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) induced the expression of IL-21 predominantly in CD4+ T cells. A fraction of IL-21-expressing CD4+ T cells simultaneously expressed Th1 cytokines but did not secrete Th2 or Th17 cytokines, suggesting that MTB-specific IL-21-expressing CD4+ T cells were different from Th1, Th2 and Th17 subpopulations. The majority of MTB-specific IL-21-expressing CD4+ T cells co-expressed IFN-γ and IL-21+IFN-γ+CD4+ T cells exhibited obviously polyfunctionality. In addition, MTB-specific IL-21-expressing CD4+ T cells displayed a CD45RO+CD62LlowCCR7lowCD40LhighICOShigh phenotype. Bcl-6-expression was significantly higher in IL-21-expressing CD4+ T cells than IL-21-CD4+ T cells. Moreover, IL-12 could up-regulate MTB-specific IL-21 expression, especially the frequency of IL-21+IFN-γ+CD4+ T cells. Taken together, our results demonstrated that MTB-specific IL-21+IFN-γ+CD4+ T cells from local sites of tuberculosis (TB) infection could be enhanced by IL-12, which have the features of both Tfh and Th1 cells and may have an important role in local immune responses against TB infection.

Highlights

  • Tuberculosis (TB) is one of the most ancient diseases of mankind and currently remains a leading cause of death from infectious disease worldwide [1,2,3]

  • To determine whether the Mycobacterium tuberculosis (MTB)-specific peptides early secreted antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) (E/C) induce IL-21 production, pleural fluid cells (PFCs) were cultured in the presence of medium alone, E/C peptides, or PMA plus ionomycin

  • PMA plus ionomycin induced a stronger response. These results indicated that E/C peptides induced IL21 production by PFCs at both mRNA and protein levels

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Summary

Introduction

Tuberculosis (TB) is one of the most ancient diseases of mankind and currently remains a leading cause of death from infectious disease worldwide [1,2,3]. Tfh cells are considered to be a distinct CD4+ T cell type and they are important for protective immunity [24,26]. Those cells are characterized by expression of the transcription factor B-cell lymphoma 6 (Bcl-6), production of high amounts of the B-cell stimulatory cytokine IL-21, and increased levels of CXCR5, inducible costimulator (ICOS) and programmed death 1 (PD-1) [24,26,27]. We tried to define the relationship between MTB-specific IL21-expressing cells and Tfh cells. Our data demonstrated that MTB-specific IL-21-expressing CD4+ T cells are present at local sites of infection in patients with tuberculous pleurisy (TBP) and these cells may play an important role in local cellular immunity against TB infection

Results
Discussion
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