Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
The immune suppressive properties of mesenchymal stem cells (MSC) have garnered increasing attention over past decades. Human umbilical cord-derived MSC (UC-MSC) share similar immunosuppressive functions as bone marrow-derived MSC (BM-MSC). Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by extraglandular abnormalities and overproduction of antibodies. Previous studies showed that MSC transplantation were effective both in an animal model and SS patients. However, the underlining mechanism remains largely unknown. The aim of this study is to investigate whether UC-MSC might suppress the generation of T follicular helper (Tfh) cells in SS.
Methods: The percentages of CXCR5+PD-1+CD4+ cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMC) from SS patients and healthy controls. The correlation between frequencies of Tfh cells and levels of total IgG, anti-Ro/SSA and anti-La/SSB in SS patients were assessed. PBMC of SS patients in the presence or absence of PHA were cultured with UC-MSC supernatant or UC-MSC at a ratio of 1 to 1, 1 to 10 or 1 to 100 in a cell-to-cell contact or transwell system for 3 days. CD4+ naïve T cells were isolated from SS PBMC and then co-cultured with or without UC-MSC under Tfh-skewing condition for 2 days (for RT-PCR) or 4 days (for FACS). CD4+ T cells were isolated from SS PBMC and labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) and then co-cultured with or without UC-MSC in the presence of anti-CD3/CD28 for 4 days. The percentages of CXCR5+PD-1+CD4+ T cells were tested by flow cytometry.
Results:
We showed that the circulating percentage of CXCR5+PD-1+CD4+ cells in SS patients were significantly higher than in healthy controls, and positively correlated with levels of anti-La/SSB but not with total IgG or anti-Ro/SSA. UC-MSC inhibited the generation of Tfh cells in PHA-stimulated PBMC dose-dependently in vitro. The differentiation and proliferation of Tfh cells were blocked by UC-MSC significantly and this suppression was mediated by UC-MSC-secreted soluble factors. RT-PCR showed that UC-MSC suppression of Tfh cells was dependent on indoleamine 2, 3-dioxygenase (IDO). Furthermore, UC-MSC supernatant was also able to inhibit the generation of Tfh cells in SS.
Conclusion:
These results suggest that Tfh cells may play a pathogenic role in SS. UC-MSC inhibition of Tfh cells may be a potential mechanism for the therapeutic effect of MSC in SS.
Disclosure:
R. Liu,
None;
M. Zhou,
None;
D. Su,
None;
X. Li,
None;
L. Sun,
None.
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