Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production

Zhang, X., Lindwall, E., Gauthier, C., Lyman, J., Spencer, N., Alarakhia, A., Fraser, A., Ing, S., Chen, M., Webb-Detiege, T., Zakem, J., Davis, W., Choi, Y. S. and Quinet, R. (2015) Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production. Lupus, 24 9: 909-917. doi:10.1177/0961203314567750


Author Zhang, X.
Lindwall, E.
Gauthier, C.
Lyman, J.
Spencer, N.
Alarakhia, A.
Fraser, A.
Ing, S.
Chen, M.
Webb-Detiege, T.
Zakem, J.
Davis, W.
Choi, Y. S.
Quinet, R.
Title Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production
Formatted title
Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production
Journal name Lupus   Check publisher's open access policy
ISSN 1477-0962
0961-2033
Publication date 2015-08-25
Sub-type Article (original research)
DOI 10.1177/0961203314567750
Open Access Status Not Open Access
Volume 24
Issue 9
Start page 909
End page 917
Total pages 9
Place of publication London, United Kingdom
Publisher SAGE Publications
Collection year 2016
Language eng
Formatted abstract
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLE patients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupus patients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity.

Methods: Peripheral blood was collected from 29 lupus patients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA.

Results: The frequency of circulating Tfh-like cells was significantly increased in SLE patients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA.

Conclusion: The accumulated circulating Tfh-like cells in lupus patients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.
Keyword Autoantibody production
Follicular helper T cells
Germinal center
Interleukin 21
Systemic lupus erythematosus
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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