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Association of circulating SLAMF7+Tfh1 cells with IgG4 levels in patients with IgG4-related disease.
- Source :
- BMC Immunology; 6/1/2020, Vol. 21 Issue 1, p1-10, 10p
- Publication Year :
- 2020
-
Abstract
- Background: Follicular helper CD4<superscript>+</superscript> T (Tfh) cells have a critical role in IgG4 production by B cells in IgG4-related disease (IgG4-RD). Recent studies including ours showed that SLAMF7<superscript>+</superscript>CD4<superscript>+</superscript> T cells are an important pathological driver of IgG4-RD. In this study, we have sought to elucidate a relationship between helper CD4<superscript>+</superscript> T (Th), particularly Tfh, cells and SLAMF7<superscript>+</superscript> CD4<superscript>+</superscript> T cells in IgG4-RD. Results: The patients with IgG4-RD enrolled in this study were aged 66 ± 12 years and their titers of serum IgG4 were 372 ± 336 mg/dl. Th1 cells, activated circulating Tfh1 (cTfh1), and activated cTfh2 cells increased in IgG4-RD. SLAMF7 was mainly expressed on Th1 and cTfh1, but not cTfh2, cells in the patients. SLAMF7<superscript>+</superscript> cTfh1 cells were PD-1/CD28 double-positive, whereas SLAMF7<superscript>+</superscript> Th1 cells were CD28 negative. Positive correlations were noted between serum IgG4 levels and the number of activated cTfh2 cells and SLAMF7<superscript>+</superscript> cTfh1 cells, but not SLAMF7<superscript>+</superscript> Th1 cells. Intriguingly, among cTfh1 cells, activated SLAMF7<superscript>+</superscript> cTfh1 cells were high producers of IL-10 along with IL-21. Blimp-1, but not Bcl-6, mRNA was expressed at high levels in activated SLAMF7<superscript>+</superscript> cTfh1 cells. In addition to CD4<superscript>+</superscript> T cells, the frequency of SLAMF7<superscript>+</superscript> fraction was higher in memory B cells than naïve B cells in patients with IgG4RD. Finally, upon stimulation via B-cell receptor and CD40, Tfh1-associated cytokines, IL-21 and IFN-γ, most significantly induced SLAMF7 expression in memory B cells. Conclusions: Together, these results suggest that circulating SLAMF7<superscript>+</superscript> Tfh1 cells, along with Tfh2 cells, play a pathologic role in IgG4 production in IgG4-RD. [ABSTRACT FROM AUTHOR]
- Subjects :
- TH1 cells
B cells
T helper cells
T cells
CELLS
Subjects
Details
- Language :
- English
- ISSN :
- 14712172
- Volume :
- 21
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- BMC Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 143542152
- Full Text :
- https://doi.org/10.1186/s12865-020-00361-0