T Cells and T-Cell Cytokine Transcripts in the Synovial Membrane in Patients with Osteoarthritis

American Society for Microbiology - Tập 5 Số 4 - Trang 430-437 - 1998
Lazaros I. Sakkas1, Carla R. Scanzello1, Norman A. Johanson2, Janet Burkholder3, Amit Mitra4, Padmini Salgame1, Christos D. Katsetos1, Chris D. Platsoucas1
1Department of Microbiology and Immunology,1
2Department of Orthopedic Surgery,2
3Section of Rheumatology, Department of Medicine,3 and
4Section of Plastic Surgery, Department of Surgery,4Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Tóm tắt

ABSTRACT

The synovial membrane in osteoarthritis (OA) often exhibits inflammatory infiltrates, but the role of T cells in these infiltrates is not known. T-cell activation antigens were analyzed by immunohistochemistry, and T-cell cytokine transcripts were measured by competitive PCR in synovial membranes from patients with OA and rheumatoid arthritis (RA). Lymphoid cell aggregates, containing primarily CD3+T lymphocytes, were found in 65% of patients with OA. Mononuclear cells expressing the activation antigens CD69, CD25, CD38, CD43, CD45RO, and HLA class II were present in both patient groups, although in higher numbers in patients with RA. Interleukin 2 (IL-2) transcripts were found in 10 of 18 patients with OA versus 12 of 13 patients with RA (P= 0.03). Gamma interferon (IFN-γ) transcripts were detected in 9 of 18 patients with OA versus 10 of 13 patients with RA (not significant), whereas IL-10 transcripts were found in nearly all patients. IL-4 and IL-5 were not detected in any patients. The levels of IFN-γ and IL-2 transcripts, normalized for T-cell number equivalents, were not statistically different between OA and RA, but the levels of IFN-γ, normalized for total cell number equivalents, were lower in OA than in RA (P= 0.01). Synovial membranes that expressed IL-2 and IFN-γ transcripts were more likely to have heavier infiltrations of T cells and cells bearing activation markers than synovial membranes that did not express these cytokines. The presence of activated T cells and TH1 cytokine transcripts in chronic joint lesions of patients with OA suggests that T cells contribute to chronic inflammation in a large proportion of these patients.

Từ khóa


Tài liệu tham khảo

Akbar A. N. Terry L. Timms A. Beverley P. C. Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J. Immunol. 140 1988 2171 2178

10.1002/art.1780331004

Altman D. G. Practical statistics for medical research. 1991 Chapman & Hall London England

10.1002/art.1780310302

10.1111/j.1365-2249.1996.tb08288.x

10.1016/0003-2697(87)90021-2

10.1002/art.1780340908

10.1093/rheumatology/35.1.24

10.1002/art.1780391204

10.1002/eji.1830241037

Firestein G. S. Alvaro-Garcia J. M. Maki R. Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J. Immunol. 144 1990 3347 3353

10.1128/iai.64.7.2523-2531.1996

10.1084/jem.183.6.2559

10.1073/pnas.87.7.2725

Goldenberg D. L. Egan M. S. Cohen A. S. Inflammatory synovitis in degenerative joint disease. J. Rheumatol. 9 1982 204 209

10.1016/S0021-9258(19)84486-1

10.1002/art.1780340205

Howel D. S. Pelletier J.-P. Etiopathogenesis of osteoarthritis Arthritis and allied conditions. McCarty D. J. Koopman W. J. 1993 1723 1734 Lea & Febiger Philadelphia Pa

Jackson D. G. Bell J. I. Isolation of a cDNA encoding the human CD38(T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. J. Immunol. 144 1990 2811 2815

10.1002/art.1780400209

10.1136/ard.51.6.731

10.1084/jem.179.5.1517

10.1136/jcp.41.8.847

Khoury S. J. Hancock W. W. Weiner H. L. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor β, interleukin 4, and prostaglandin E expression in the brain. J. Exp. Med. 176 1992 1355 1364

Klimiuk P. A. Goronzy J. J. Bjornsson J. Beckenbaugh A. Weyand C. M. Tissue cytokine patterns distinguish variants of rheumatoid synovitis. Am. J. Pathol. 151 1997 1311 1319

10.1006/clin.1995.1157

10.1073/pnas.92.21.9510

10.1002/art.1780301001

10.1038/34814

10.1084/jem.174.5.1209

10.1084/jem.177.4.1199

Matzkin E. and R. Winchester. 1984. Heterogeneity of cell populations in osteoarthritis cartilage as detected by monoclonal antibodies. Arthritis Rheum. 27 (Suppl. 4) : S36.

10.1111/j.1365-3083.1992.tb03260.x

Miltenburg A. M. M. Lacraz S. Welgus H. G. Dayer J.-M. Immobilized anti-CD3 antibody activates T cell clones to induce the production of interstitial collagenase, but not tissue inhibitor of metalloproteinases, in monocytic THP-1 cells and dermal fibroblasts. J. Immunol. 154 1995 2655 2667

10.1002/art.1780350805

Mollenhauer J. van der Mark K. Burmester G. R. Gluckert K. Lutjen-Drecoll E. Brune K. Serum autoantibodies against chondrocyte cell surface proteins in osteoarthritis and rheumatoid arthritis. J. Rheumatol. 15 1988 1811 1817

Moskowitz R. W. Clinical and laboratory findings in osteoarthritis Arthritis and allied conditions. McCarty D. J. Koopman W. J. 1993 1735 1760 Lea & Febiger Philadelphia Pa

10.1016/0092-8674(94)90332-8

10.1016/S0889-857X(21)00331-8

Pelletier J.-P. Martel-Pelletier J. Howel D. S. Etiopathogenesis of osteoarthritis Arthritis and allied conditions. Koopman W. J. 1997 1969 1984 Williams & Wilkins Baltimore Md

10.1084/jem.173.6.1501

10.1111/j.1365-3083.1993.tb01696.x

10.1172/JCI1422

10.1084/jem.178.1.87

10.1136/ard.47.4.300

10.1007/BF02918273

Sakkas L. I. Johanson N. A. Burkholder J. Mitra A. Scanzello C. Salgame P. Platsoucas C. D. TH1/TH2 cytokines in synovial membranes of rheumatoid arthritis and osteoarthritis: IL-12 may influence TH1 pattern. FASEB J. 10 1996 A1353

10.1126/science.254.5029.279

Schaak J. F. Pfers I. Meyer zum Buschenfelde K. H. Different cytokine profiles in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis and seronegative spondyloarthropathies. Clin. Exp. Rheumatol. 14 1996 155 162

10.1136/ard.54.7.560

10.1073/pnas.91.18.8562

10.1016/S0049-0172(95)80020-4

Smith M. D. Triantafillou S. Parker A. Youssef P. P. Coleman M. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J. Rheumatol. 24 1997 365 371

Sugiyama E. Kuroda A. Taki H. Ikemoto M. Hori T. Yamashita N. Maruyama M. Kobayashi M. Interleukin-10 co-operates with interleukin-4 to suppress inflammatory cytokine production by freshly prepared adherent rheumatoid synovial cells. J. Rheumatol. 22 1995 2020 2026

10.1006/clin.1995.1149

Testi R. Phillips J. H. Lanier L. L. Leu 23 induction as an early marker of functional CD3/T cell antigen receptor triggering. J. Immunol. 142 1989 1854 1860

10.1136/ard.54.8.654

10.1111/j.1365-3083.1992.tb03148.x

10.1007/BF01330295

Warren C. J. Howell W. M. Bhambhani M. Cawley M. I. Smith J. L. An investigation of T-cell subset phenotype and function in the rheumatoid synovium using in situ hybridization for IL-2 mRNA. Immunology 72 1991 250 255

Windhagen A. Anderson D. E. Carrizosa A. Williams R. E. Hafler D. A. IL-12 induces human T cells secreting IL-10 with IFN-γ. J. Immunol. 157 1996 1127 1131

10.1126/science.254.5029.277