Circulating TFH subset distribution is strongly affected in lupus patients with an active disease

PLoS One. 2013 Sep 19;8(9):e75319. doi: 10.1371/journal.pone.0075319. eCollection 2013.


Follicular helper T cells (TFH) represent a distinct subset of CD4(+) T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-)CCR6(+)), TFH1 (CXCR3 (+) CCR6(-)) or TFH2 (CXCR3(-)CCR6(-)) cells among CXCR5 (+) CD45RA(-)CD4(+) T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI score>8), while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-)IgD(-)CD19(+) cells) expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD4 Lymphocyte Count
  • CD5 Antigens / metabolism
  • Case-Control Studies
  • Cytokines / biosynthesis
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunologic Memory
  • Immunophenotyping
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Middle Aged
  • Phenotype
  • Receptors, CXCR5 / metabolism
  • Receptors, Interleukin-21 / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Young Adult


  • CD5 Antigens
  • Cytokines
  • Receptors, CXCR5
  • Receptors, Interleukin-21
  • Immunoglobulin E

Grants and funding

This study was supported by the French Centre National de la Recherche Scientifique (CNRS), by grants from the Fondation Athritis-Courtin and from the Hôpitaux Universitaires de Strasbourg (PHRC). The funders had no role in study design, data collection and analysis, decision to publish, or presentation of the manuscript.