• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. Oct 2005; 64(10): 1474–1479.
Published online Apr 7, 2005. doi:  10.1136/ard.2004.031781
PMCID: PMC1755251

Salivary gland and peripheral blood T helper 1 and 2 cell activity in Sjögren's syndrome compared with non-Sjögren's sicca syndrome


Objectives: To investigate whether differences in T helper (Th) 1 and Th2 cell activity in salivary glands ("local") or ("peripheral") blood can discriminate between Sjögren's syndrome (SS) and non-Sjögren's sicca syndrome (nSS-sicca). Additionally, to study relationships of local and peripheral Th cell activities with each other and with disease activity measures.

Methods: 62 sicca patients (32 with SS, 30 with nSS-sicca) were studied. Local Th1 (interferon γ (IFNγ)) and Th2 (interleukin (IL) 4) activity were determined using immunohistochemistry. T cell production of IFNγ and IL4 in peripheral blood (PB) was determined by ELISA. Erythrocyte sedimentation rate (ESR) and serum IgG were considered disease activity measures.

Results: ESR and serum IgG were higher in patients with SS than in patients with nSS-sicca. Local Th1 cell activity was higher and PB Th1 activity lower in patients with SS than in those with nSS-sicca. Th2 cell activity did not differ significantly between the patient groups. The ratio IFNγ/IL4 was higher in salivary glands and lower in PB in patients with SS than in patients with nSS-sicca. Local and peripheral Th1 and Th2 cell activities correlated with ESR and serum IgG levels. ESR, serum IgG, and local or peripheral Th1 or Th2 cell activity did not discriminate between patients with SS and nSS-sicca.

Conclusions: An imbalance between Th1 and Th2 activity in sicca patients is clearly related to the severity of disease, but cannot be used to distinguish between patients with SS and those with nSS-sicca.

Full Text

The Full Text of this article is available as a PDF (98K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kruize AA, Hené RJ, van der Heide A, Bodeutsch C, de Wilde PC, van Bijsterveld OP, de Jong J, Feltkamp TE, Kater L, Bijlsma JW. Long-term followup of patients with Sjögren's syndrome. Arthritis Rheum. 1996 Feb;39(2):297–303. [PubMed]
  • Pertovaara M, Korpela M, Uusitalo H, Pukander J, Miettinen A, Helin H, Pasternack A. Clinical follow up study of 87 patients with sicca symptoms (dryness of eyes or mouth, or both). Ann Rheum Dis. 1999 Jul;58(7):423–427. [PMC free article] [PubMed]
  • Skopouli FN, Fox PC, Galanopoulou V, Atkinson JC, Jaffe ES, Moutsopoulos HM. T cell subpopulations in the labial minor salivary gland histopathologic lesion of Sjögren's syndrome. J Rheumatol. 1991 Feb;18(2):210–214. [PubMed]
  • Romagnani S. Lymphokine production by human T cells in disease states. Annu Rev Immunol. 1994;12:227–257. [PubMed]
  • Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996 Mar;17(3):138–146. [PubMed]
  • Ohyama Y, Nakamura S, Matsuzaki G, Shinohara M, Hiroki A, Fujimura T, Yamada A, Itoh K, Nomoto K. Cytokine messenger RNA expression in the labial salivary glands of patients with Sjögren's syndrome. Arthritis Rheum. 1996 Aug;39(8):1376–1384. [PubMed]
  • Mitsias DI, Tzioufas AG, Veiopoulou C, Zintzaras E, Tassios IK, Kogopoulou O, Moutsopoulos HM, Thyphronitis G. The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren's syndrome. Clin Exp Immunol. 2002 Jun;128(3):562–568. [PMC free article] [PubMed]
  • Hagiwara E, Pando J, Ishigatsubo Y, Klinman DM. Altered frequency of type 1 cytokine secreting cells in the peripheral blood of patients with primary Sjögren's syndrome. J Rheumatol. 1998 Jan;25(1):89–93. [PubMed]
  • Kohriyama K, Katayama Y. Disproportion of helper T cell subsets in peripheral blood of patients with primary Sjögren's syndrome. Autoimmunity. 2000;32(1):67–72. [PubMed]
  • Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002 Jun;61(6):554–558. [PMC free article] [PubMed]
  • Thepen T, Langeveld-Wildschut EG, Bihari IC, van Wichen DF, van Reijsen FC, Mudde GC, Bruijnzeel-Koomen CA. Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: an immunocytochemical study. J Allergy Clin Immunol. 1996 Mar;97(3):828–837. [PubMed]
  • Verhoef CM, Van Roon JA, Vianen ME, Glaudemans CA, Lafeber FP, Bijlsma JW. Lymphocyte stimulation by CD3-CD28 enables detection of low T cell interferon-gamma and interleukin-4 production in rheumatoid arthritis. Scand J Immunol. 1999 Oct;50(4):427–432. [PubMed]
  • Fox RI, Kang HI, Ando D, Abrams J, Pisa E. Cytokine mRNA expression in salivary gland biopsies of Sjögren's syndrome. J Immunol. 1994 Jun 1;152(11):5532–5539. [PubMed]
  • Konttinen YT, Kemppinen P, Koski H, Li TF, Jumppanen M, Hietanen J, Santavirta S, Salo T, Larsson A, Hakala M, et al. T(H)1 cytokines are produced in labial salivary glands in Sjögren's syndrome, but also in healthy individuals. Scand J Rheumatol. 1999;28(2):106–112. [PubMed]
  • Morita Y, Yamamura M, Kawashima M, Harada S, Tsuji K, Shibuya K, Maruyama K, Makino H. Flow cytometric single-cell analysis of cytokine production by CD4+ T cells in synovial tissue and peripheral blood from patients with rheumatoid arthritis. Arthritis Rheum. 1998 Sep;41(9):1669–1676. [PubMed]
  • van Roon JA, Verhoef CM, van Roy JL, Gmelig-Meyling FH, Huber-Bruning O, Lafeber FP, Bijlsma JW. Decrease in peripheral type 1 over type 2 T cell cytokine production in patients with rheumatoid arthritis correlates with an increase in severity of disease. Ann Rheum Dis. 1997 Nov;56(11):656–660. [PMC free article] [PubMed]

Figures and Tables

Figure 1
 ESR and serum IgG of 30 patients with nSS-sicca and 32 patients with SS. The solid line represents the median value, the boxes stretch from the lower 25th centile to the upper 75th centile. Values of p for differences between the SS and non-SS ...
Figure 3
 Relations between measures of disease activity and IFNγ profiles. (A, B) depict the relation between SG IFNγ+ T cells (number/0.04 mm2) and ESR (A) and serum IgG (B). (C, D) depict the relation between PB T cell IFNγ ...
Figure 5
 Cytokine ratio profiles related to measures of disease activity. (A, B) depict the relation of SG IFNγ/IL4 positive T cells with ESR (A) and serum IgG (B). (C, D) depict the relation of PB T cell IFNγ/IL4 production (x1000) with ...
Figure 2
 SG and PB cytokine profile for patients with nSS-sicca and SS (n = 30 and 32 patients, respectively). The solid line represents the median value, the boxes stretch from the lower 25th centile to the upper 75th centile. (A, B, C) SG number of ...
Figure 4
 Relations between measures of disease activity and IL4 profiles. (A, B) depict the relation between SG IL4+ T cells (number/0.04 mm2) and ESR (A) and serum IgG (B). (C, D) depict the relation between PB T cell IL4 production (pg/ml) and ESR ...

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...