Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Salivary Gland Epithelial Cells Are Capable to Directly Induce the Differentiation of IL-21-Secreting Follicular Helper CD4 T Cells in Primary Sjgren's Syndrome.
Gong1, Yazhuo, Alsaleh2, Ghada, Chatelus3, Emmanuel, Sordet4, Christelle, Sibilia5, Jean, Wachsmann1, Dominique, Gottenberg2, Jacques-Eric
EA 44 38, Strasbourg, France
Strasbourg University Hospital, Strasbourg, France
Hopital Hautepierre, Strasbourg, France
Hautepierre Strasbourg Hospital University, Strasbourg, France
CHU Hautepierre, Strasbourg, France
Follicular helper CD4 T lymphocytes (Tfh) play a pivotal role in the activation of B lymphocytes, notably through IL-21 secretion. An increase in blood proportion of Tfh was recently reported in primary Sjögren's syndrome (pSS). Salivary gland epithelial cells (SGEC) of patients with pSS express various molecules implicated in innate and acquired immune responses and can act as antigen-presenting cells. We therefore investigated whether SGECs were capable to differentiate naïve T cells into follicular helper T cells.
Primary culture of salivary epithelial cells was derived from minor salivary gland biopsies isolated from patients with SS or controls (subjects complaining from dry symptoms without any feature of autoimmunity).
Expression of ICOSL by SGECs after stimulation with poly I:C was assessed using qPCR. Naïve T cells were cocultured with SGECs and activated by anti-CD2, anti-CD3 and anti-CD28. Expression of ICOS and CXCR5 was analyzed using flow cytometry. Levels of IL-21, Il-6 and IL-17 were assessed in culture supernatants.
SGECs of patients pSS (n=4) or controls (n=4) both up-regulated the expression of ICOSL when stimulated with poly I:C, but did not secrete IL-21. Coculture between T cells and non stimulated SGECs (1 pSS, 2 SS and 3 controls) induced the increased expression of CXCR5 (MFI 6.5 versus 5.2, p=0.09) and ICOS (MFI 41.25±14.8 versus 15.75±1.26, p=0.005). 3.76±2.05% on average (n=6) CXCR5+ICOS+ T cells were differentiated by coculture with SGECs. Secretion of IL-21 was also significantly increased after coculture (671.8±394.6 versus 17.8±19.5 pg/ml in CD4 T cells alone and 0 pg/ml in SGECs alone, p=0.0004). Secretion of IL-17, a cytokine that can be secreted by Tfh, was detected in the supernatant of cocultures (57±49.2 pg/ml) but not in the supernatant of SGEC or in T naive alone (p=0.0004). No significant change was observed in ICOS or CXCR5 expression using or not a transwell for cocultures.. However, coculture with a transwell partly inhibited IL-21(198.6±83.3 pg/ml with a transwell versus 591.4±308.9 pg/ml without, p=0.0286) and completely inhibited IL-17 secretion.
We demonstrated that SGEC are capable to directly induce the differentiation of IL-21 secreting follicular helper T cells, which might contribute to the marked activation of B lymphocytes in salivary glands. Further analyses are ongoing to determine the pathways implicated in this differentiation, which may involve IL-12. These results emphasize the pivotal role of salivary gland epithelial cells in this autoimmune epithelitis and suggest that follicular helper T cells and IL-21 might represent relevant therapeutic targets in pSS.
To cite this abstract, please use the following information:
Gong, Yazhuo, Alsaleh, Ghada, Chatelus, Emmanuel, Sordet, Christelle, Sibilia, Jean, Wachsmann, Dominique, et al; Salivary Gland Epithelial Cells Are Capable to Directly Induce the Differentiation of IL-21-Secreting Follicular Helper CD4 T Cells in Primary Sjgren's Syndrome. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :774