Analysis of the T-cell receptor Valpha repertoire and cytokine gene expression in Sjogren's syndrome

Abstract

The antigen receptor diversity of pathogenic T cells in Sjögren's syndrome (SS) may have important implications in the development of the disease; cytokines from these cells and other sources also play a role in the pathogenesis of this disease. Using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique, we have attempted to correlate the presence of restriction in the T-cell receptor (TCR) repertoire with cytokine profiles. We have analysed TCR V alpha family usage, and the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), in labial biopsies from 12 patients with SS and compared these with samples from three patients with chronic sialadenitis (CS). Only one of the SS biopsies showed evidence of V alpha restriction (three out of 18 gene families). Apart from this, expression patterns were similar in both patient groups. Four of the 12 SS samples demonstrated a 'limited heterogeneity' of the V alpha repertoire with 3-4 families predominantly expressed, in particular V alpha1 and V alpha3. Peripheral blood lymphocytes were unrestricted. The cytokine profiles of the SS and CS biopsies were generally similar. However both IFN-gamma and IL-1alpha were absent from CS, but present in SS samples. The expression of IFN-gamma in the majority of the samples, together with a lack of IL-4 and IL-13 mRNA, suggests the predominance of a Th1 response in SS. There was no clear association between the repertoire of V alpha genes expressed and the cytokine profile observed. However, the V alpha restriction in one SS sample did correspond with a limited diversity of cytokines detected.

Chronic pancreatitis, pseudotumors and other tumor-like lesions

“…6,90 Increased numbers of these T cells bearing HLA-DR were also found in the peripheral blood. 107 Subtyping of the CD4 þ cells according to their cytokine production profiles revealed a predominance of CD4 þ Th1 cells over Th2 cells in some cases, 107 similar to what has been reported in Sjö gren's disease 108 and primary sclerosing cholangitis. 109 HLA-DR antigens have also been detected on pancreatic duct cells.…”

CD1d-Independent Developmental Acquisition of Prompt IL-4 Gene Inducibility in Thymus CD161(NK1)−CD44lowCD4+CD8− T Cells Is Associated with Complementarity Determining Region 3-Diverse and Biased Vβ2/Vβ7/Vβ8/Vα3.2 T Cell Receptor Usage

“…In addition, T cell clones derived from the CNS from multiple sclerosis patients preferentially express V␤6 and produce large amounts of proinflammatory cytokines (82). Similar findings of skewed TCR family usage have also been reported for Kawasaki disease and Sjogren's syndrome (83,84). It is unknown at this time whether the biased usage of V␤(2/7/8) and V␣3.2 by CD161 Ϫ CD44 low CD4 ϩ CD8 Ϫ T cells capable of IL-4 inducibility is involved in the cause and/or manifestation of disease states, but the fact that common strains of mice fall into two levels of IL-4 inducibility (Fig.…”

Professional Antigen Presenting Cells in Minor Salivary Glands in Sjögren's Syndrome: Potential Contribution to the Histopathological Diagnosis?

“…Interestingly, TNF-␣ mRNA and protein expression have been detected in the MSG of patients with Sjögren's syndrome, as well as in those of healthy volunteers. The highest levels were detected in patients with Sjögren's syndrome (Ajjan et al, 1998;Oxholm et al, 1992;Sun et al, 1998). The expression of CD1a on DC in MSG in which a lymphocytic infiltrate has developed may be the result of the production of the proinflammatory cytokine TNF-␣ by infiltrating cells.…”