The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren's syndrome

Clinical and Experimental Immunology - Tập 128 Số 3 - Trang 562-568 - 2002
Dimitris I. Mitsias1, Athanasios G. Tzioufas1, CI Veiopoulou1, Ηλίας Ζιντζαράς2, Ioannis Tassios1, Olga Kogopoulou1, H M Moutsopoulos1, Georges Thyphronitis1
1Department of Pathophysiology, Medical School, University of Athens, Greece
2Hellenic Organization for Medicines, Athens, Greece

Tóm tắt

SUMMARYExpression of type-1 and type-2 cytokines at the mRNA level in labial salivary glands (LSG) of patients with Sjogren's syndrome (SS), as reported by several groups, have generated conflicting results. In the present study we have directly examined the production of IL-4, IL-13 and IFN-γ by lymphocytes infiltrating the LSG of 44 consecutive patients referred for SS evaluation. Cytokines production was evaluated following in vitro culture of LSG in the presence of IL-2. IFN-γ and IL-13 were detected in the majority of SN (24/44 and 26/44, respectively) while IL-4 was present in 5/44 SN. The presence of IFN-γ was significantly higher in SS patients, as opposed to patients who did not fulfil the criteria for SS (P < 0·01). In addition, almost all cultured lymphocytes expressed mRNA for IFN-γ (17/19 cultures) and IL-13 (18/19) while IL-4 mRNA was also expressed at high frequency (14/19 cultures). Interestingly, the IFN-γ mRNA copies in cultured lymphocytes correlated significantly with the intensity of lymphocytic infiltration as evaluated by Chisholm's score (P < 0·01). Furthermore, RT-PCR of RNA extracted from whole LSG from 14 SS patients also demonstrated the presence of all cytokines in the majority of the cases and the prevalence of IFN-γ in LSG with high-grade infiltration. Because IL-13 was produced by the majority of the cultured LSG, IgE production was also evaluated. Interestingly, IgE was detected in 21/44 LSG culture SN and mainly in those biopsies that had Chisholm's score less than 0·5 (P < 0·05). We conclude that lymphocytes infiltrating the LSG are capable of producing both Th1 and Th2 cytokines and that the balance between them shifts in favour of Th1 in LSG with high infiltration score and in patients with SS.

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Tài liệu tham khảo

Moutsopoulos, 1998, Harrison's principles of internal medicine, 14th, 2001

Moutsopoulos, 1986, HLA-DR expression by labial minor salivary gland tissues in Sjogren's syndrome, Ann Rheum Dis, 45, 677, 10.1136/ard.45.8.677

Fox, 1992, Pathogenesis of Sjogren's syndrome, Rheum Dis Clin North Am, 18, 517, 10.1016/S0889-857X(21)00314-8

Skopouli, 1991, T cell subpopulations in the labial minor salivary gland histopathologic lesion of Sjogren's syndrome, J Rheumatol, 18, 210

Kong, 1997, Fas and Fas ligand expression in the salivary glands of patients with primary Sjogren's syndrome, Arthritis Rheum, 40, 87, 10.1002/art.1780400113

Abbas, 1996, Functional diversity of helper T lymphocytes, Nature, 383, 787, 10.1038/383787a0

Romagnani, 1997, The Th1/Th2 paradigm, Immunol Today, 18, 263, 10.1016/S0167-5699(97)80019-9

Liblau, 1995, Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases, Immunol Today, 16, 34, 10.1016/0167-5699(95)80068-9

Das, 1997, Autopathogenic T helper cell type 1 (Th1) and protective Th2 clones differ in their recognition of the autoantigenic peptide of myelin proteolipid protein, J Exp Med, 186, 867, 10.1084/jem.186.6.867

Pakala, 1997, T helper 2 (Th2) T cells induce acute pancreatitis and diabetes in immune-compromised nonobese diabetic (NOD) mice, J Exp Med, 186, 299, 10.1084/jem.186.2.299

Lafaille, 1997, Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease, J Exp Med, 186, 307, 10.1084/jem.186.2.307

Laman, 1998, Balancing the Th1/Th2 concept in multiple sclerosis, Immunol Today, 19, 489, 10.1016/S0167-5699(98)01320-6

Takahashi, 1996, Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice, J Clin Invest, 97, 1597, 10.1172/JCI118584

Peng, 1997, Roles of interferon-gamma and interleukin-4 in murine lupus, J Clin Invest, 99, 1936, 10.1172/JCI119361

Funauchi, 1998, Decreased Th1-like and increased Th2-like cells in systemic lupus erythematosus, Scand J Rheumatol, 27, 219, 10.1080/030097498440859

Akahoshi, 1999, Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus, Arthritis Rheum, 42, 1644, 10.1002/1529-0131(199908)42:8<1644::AID-ANR12>3.0.CO;2-L

Fox, 1994, Cytokine mRNA expression in salivary gland biopsies of Sjogren's syndrome, J Immunol, 152, 5532, 10.4049/jimmunol.152.11.5532

Ajjan, 1998, Analysis of the T-cell receptor Valpha repertoire and cytokine gene expression in Sjogren's syndrome, Br J Rheumatol, 37, 179, 10.1093/rheumatology/37.2.179

Kolkowski, 1999, Th1 predominance and perforin expression in minor salivary glands from patients with primary Sjogren's syndrome, J Autoimmun, 13, 155, 10.1006/jaut.1999.0289

Konttinen, 1999, T (H) 1 cytokines are produced in labial salivary glands in Sjogren's syndrome, but also in healthy individuals, Scand J Rheumatol, 28, 106, 10.1080/030097499442577

Fox, 1999, Cytokine expression in human labial minor salivary gland epithelial cells in health and disease, Arch Oral Biol, 44, S49, 10.1016/S0003-9969(99)90018-3

Matsumoto, 1999, Single cell analysis of T cells infiltrating labial salivary glands from patients with Sjogren's syndrome, Int J Mol Med, 4, 519

Boumba, 1995, Cytokine mRNA expression in the labial salivary gland tissues from patients with primary Sjogren's syndrome, Br J Rheumatol, 34, 326, 10.1093/rheumatology/34.4.326

De Vita, 1995, Local cytokine expression in the progression toward B cell malignancy in Sjogren's syndrome, J Rheumatol, 22, 1674

Ohyama, 1996, Cytokine messenger RNA expression in the labial salivary glands of patients with Sjogren's syndrome, Arthritis Rheum, 39, 1376, 10.1002/art.1780390816

Vitali, 1993, Preliminary criteria for the classification of Sjogren's syndrome. Results of a prospective concerted action supported by the European Community, Arthritis Rheum, 36, 340, 10.1002/art.1780360309

Chisholm, 1968, Labial salivary gland biopsy in Sjogren's disease, J Clin Pathol, 21, 656, 10.1136/jcp.21.5.656

McCullagh, 1989, Generalized linear models, 10.1007/978-1-4899-3242-6

Gygi, 1999, Correlation between protein and mRNA abundance in yeast, Mol Cell Biol, 19, 1720, 10.1128/MCB.19.3.1720

Ogawa, 1995, Analysis of transforming growth factor α and other cytokines in autoimmune exocrinopathy (Sjogren's syndrome), J Interferon Cytokine Res, 15, 759, 10.1089/jir.1995.15.759

Mosmann, 1996, The expanding universe of T-cell subsets: Th1, Th2 and more, Immunol Today, 17, 138, 10.1016/0167-5699(96)80606-2

Mustafa, 1998, Augmented levels of macrophage and Th1 cell-related cytokine mRNA in submandibular glands of MRL/lpr mice with autoimmune sialoadenitis, Clin Exp Immunol, 112, 389, 10.1046/j.1365-2249.1998.00609.x

Villareal, 1996, Differential interleukin (IL)-10 and IL-13 gene expression in vivo in salivary glands and peripheral blood mononuclear cells from patients with primary Sjogren's syndrome, Immunol Lett, 49, 105, 10.1016/0165-2478(95)02490-5

Haanen, 1991, Selection of a human T helper type 1-like T cell subset by mycobacteria, J Exp Med, 174, 583, 10.1084/jem.174.3.583

Yssel, 1992, T cell activation inducing epitopes of the house dust mite allergen Der p 1. Induction of a restricted cytokine production profile of Der p 1-specific T cell clones upon antigen-specific activation, J Immunol, 148, 738, 10.4049/jimmunol.148.3.738

Borish, 1997, Th1/Th2 lymphocytes: doubt some more, J Allergy Clin Immunol, 99, 161, 10.1016/S0091-6749(97)70090-3

Sarfati, 1989, IgE synthesis by chronic lymphocytic leukemia cells, J Exp Med, 170, 1775, 10.1084/jem.170.5.1775

Thyphronitis, 1989, IgE secretion by Epstein–Barr virus-infected purified human B lymphocytes is stimulated by interleukin 4 and suppressed by interferon gamma, Proc Natl Acad Sci USA, 86, 5580, 10.1073/pnas.86.14.5580

Ferraccioli, 1997, Cytokine expression in the salivary glands of Sjogren's syndrome patients in relation to tissue infiltration and lymphoepithelial lesions [letter], Arthritis Rheum, 40, 987, 10.1002/art.1780400537

Bouneaud, 2000, Impact of negative selection on the t cell repertoire reactive to a self-peptide. A large fraction of T cell clones escapes clonal deletion, Immunity, 13, 829, 10.1016/S1074-7613(00)00080-7

Malherbe, 2000, Selective activation and expansion of high-affinity CD4 (+) T cells in resistant mice upon infection with Leishmania major, Immunity, 13, 771, 10.1016/S1074-7613(00)00075-3

Blander, 2000, Alteration at a single amino acid residue in the T cell receptor alpha chain complementarity determining region 2 changes the differentiation of naive CD4 T cells in response to antigen from T helper cell type 1 (Th1) to Th2, J Exp Med, 191, 2065, 10.1084/jem.191.12.2065

Moutsopoulos, 1994, Sjogren's syndrome: autoimmune epithelitis, Clin Immunol Immunopathol, 72, 162, 10.1006/clin.1994.1123