Analysis of the T-cell receptor Valpha repertoire and cytokine gene expression in Sjögren's syndrome.
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.
Ajjan
R A
RA
Department of Medicine, University of Sheffield Clinical Sciences Centre, Northern General Hospital.
McIntosh
R S
RS
Waterman
E A
EA
Watson
P F
PF
Franklin
C D
CD
Yeoman
C M
CM
Weetman
A P
AP
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D019672:Genes, T-Cell Receptor / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism; D012793:Sialadenitis / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta