Session Title: T Cell Biology and Targets in Autoimmune Disease Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Lymphocytic aggregates in the salivary glands (SG) of Sjögren’s syndrome (SS) can organize in ectopic lymphoid structures (ELS) forming functional germinal centers (GCs), which are linked to the development of MALT lymphoma (MALT-L). T follicular-helper cells (Tfh) and follicular T regulatory cells (Tfr) are specialized CD4+ T helper cells that positively and negatively regulate, respectively, the magnitude of the GC response and possibly the development of autoimmunity. We aimed to characterize the infiltration of Tfh and Tfr in the SG of patients with SS in the presence/absence of ectopic GCs and MALT-L.
SG biopsies with matching histology and RNA from 37 SS and 38 non-specific chronic sialadenitis (NSCS) patients were stratified as ELS-/ELS+ based on CD3/CD20/CD21/CD138 immunostaining (IHC). Histological samples and mRNA from 12 parotid MALT-L were also studied. Gene expression was performed with Taqman rt-PCR. Multicolor immunofluorescence/confocal microscopy for CD3, CD4, CD45RO, ICOS, PD1, BCL6 and FoxP3 was used to identify Tfh and Tfr.
Tfh cells (CD4+CD45RO+PD1+ICOS+Bcl6+) and Tfr cells (CD4+CD45RO+PD1+ ICOS+FoxP3+) were significantly increased in the ELS+ SG tissues from SS patients vs ELS- and NSCS. Tfh cells densely infiltrated the B cell rich areas and preferentially localized within ectopic GCs in the SG tissues. Furthermore, Tfh infiltration correlated with SG IL-21 mRNA expression, which in turn was strongly correlated with CD3, CD20 and CD138 IHC scores and with CXCL13, LTb, BAFF, AID and Pax5 gene expression. Finally, MALT-L samples displayed 10-fold higher IL-21 mRNA and twice as many PD1+ICOS+BCL6+ Tfh-cells/field compared to ELS+ SS samples. The Tfh:Tfr ratio in ELS+ SG was approximately 2:1. Interestingly, while in tonsils Tfr were routinely detected within GC, in ELS+ SG Tfr were predominantly excluded from the B cell follicles and accumulated in the T cell rich areas at the periphery of the B-cell aggregates.
Within the SG of SS patients Tfh cells closely segregate with lesional IL-21 expression, localize within ELS and are strongly enriched during MALT-L development. Conversely, although Tfr cells are also present in ELS+ SG in SS patients, they are excluded from ectopic GCs. This suggests that Tfr in SS SG fail to exert their physiological immunoregulatory function in controlling the magnitude of the GC response and B cell autoreactivity, as observed in secondary lymphoid organs.
To cite this abstract in AMA style:Pontarini E, Murray Brown W, Croia C, Corsiero E, Lucchesi D, Astorri E, Sutcliffe N, Tappuni A, Pitzalis C, Bombardieri M. T Follicular-Helper CELLS (TFH) Enrichment and T Follicular-Regulatory CELLS (TFR) Exclusion from Ectopic Germinal Centers in Salivary Glands of Sjogren’s Syndrome Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/t-follicular-helper-cells-tfh-enrichment-and-t-follicular-regulatory-cells-tfr-exclusion-from-ectopic-germinal-centers-in-salivary-glands-of-sjogrens-syndrome-patients/. Accessed May 30, 2020.
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