G. Janossy, G. Panayi, O. Duke, M. Bofill, L. Poulter et al., RHEUMATOID ARTHRITIS: A DISEASE OF T-LYMPHOCYTE/MACROPHAGE IMMUNOREGULATION, The Lancet, vol.318, issue.8251, pp.839-842, 1981.
DOI : 10.1016/S0140-6736(81)91107-7

Z. Qu, C. Garcia, O. Rourke, L. Planck, S. Kohli et al., Local Proliferation of Fibroblast-Like Synoviocytes Contributes to Synovial Hyperplasia, Arthritis & Rheumatism, vol.83, issue.2, pp.212-220, 1994.
DOI : 10.1002/art.1780370210

G. Firestein and N. Zvaifler, How important are T cells in chronic rheumatoid synovitis? Arthritis Rheum, pp.768-773, 1990.

G. Panayi, J. Lanchbury, and G. Kingsley, The importance of the t cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis, Arthritis & Rheumatism, vol.141, issue.7, pp.729-735, 1992.
DOI : 10.1002/art.1780350702

G. Firestein, W. Xu, K. Townsend, D. Broide, J. Alvaro-gracia et al., Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis, Journal of Experimental Medicine, vol.168, issue.5, pp.1573-1586, 1988.
DOI : 10.1084/jem.168.5.1573

P. Miossec and W. Van-den-berg, Th1/Th2 cytokine balance in arthritis, Arthritis & Rheumatism, vol.149, issue.12, pp.2105-2115, 1997.
DOI : 10.1002/art.1780401203

P. Miossec, M. Naviliat, A. Dupuy-d-'angeac, J. Sany, and J. Banchereau, Low levels of interleukin-4 and high levels of transforming growth factor ?? in rheumatoid synovitis, Arthritis & Rheumatism, vol.168, issue.suppl 4, pp.1180-1187, 1990.
DOI : 10.1002/art.1780330819

E. Chen, E. Keystone, and E. Fish, Restricted cytokine expression in rheumatoid arthritis, Arthritis & Rheumatism, vol.367, issue.7, pp.901-910, 1993.
DOI : 10.1002/art.1780360706

A. Miltenburg, J. Van-laar, R. De-kuiper, M. Daha, and F. Breedveld, T Cells Cloned from Human Rheumatoid Synovial Membrane Functionally Represent the Th 1 Subset, Scandinavian Journal of Immunology, vol.83, issue.5, pp.603-610, 1992.
DOI : 10.1016/0165-2478(89)90052-7

A. Quayle, P. Chomarat, P. Miossec, J. Kjeldsen-kragh, O. Forre et al., Rheumatoid Inflammatory T-Cell Clones express mostly Th1 but also Th2 and Mixed (Th0-Like) Cytokine Patterns, Scandinavian Journal of Immunology, vol.35, issue.1, pp.75-82, 1993.
DOI : 10.1084/jem.177.2.523

A. Simon, E. Seipelt, and J. Sieper, Divergent T-cell cytokine patterns in inflammatory arthritis., Proceedings of the National Academy of Sciences, vol.91, issue.18, pp.8562-8566, 1994.
DOI : 10.1073/pnas.91.18.8562

Y. Morita, M. Yamamura, M. Kawashima, S. Harada, K. Tsuji et al., Flow cytometric single-cell analysis of cytokine production by CD4+ T cells in synovial tissue and peripheral blood from patients with rheumatoid arthritis, Arthritis & Rheumatism, vol.158, issue.9, pp.1669-1676, 1998.
DOI : 10.1002/1529-0131(199809)41:9<1669::AID-ART19>3.0.CO;2-G

Y. Morita, M. Yamamura, K. Nishida, S. Harada, H. Okamoto et al., Expression of interleukin-12 in synovial tissue from patients with rheumatoid arthritis, Arthritis & Rheumatism, vol.17, issue.2, pp.306-314, 1998.
DOI : 10.1002/1529-0131(199802)41:2<306::AID-ART15>3.0.CO;2-4

K. Nakamura, H. Okamura, M. Wada, K. Nagata, and T. Tamura, Endotoxin-induced serum factor that stimulates gamma interferon production, Infect Immun, vol.57, pp.590-595, 1989.

C. Dinarello, Interleukin-18, Methods, vol.19, issue.1, pp.121-132, 1999.
DOI : 10.1006/meth.1999.0837

D. Robinson, K. Shibuya, A. Mui, F. Zonin, E. Murphy et al., IGIF Does Not Drive Th1 Development but Synergizes with IL-12 for Interferon-?? Production and Activates IRAK and NF??B, Immunity, vol.7, issue.4, pp.571-581, 1997.
DOI : 10.1016/S1074-7613(00)80378-7

K. Kohno, J. Kataoka, T. Ohtsuki, Y. Suemoto, I. Okamoto et al., IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12, J Immunol, vol.158, pp.1541-1550, 1997.

M. Micallef, T. Ohtsuki, K. Kohno, F. Tanabe, S. Ushio et al., Interferon-??-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-?? production, European Journal of Immunology, vol.268, issue.7, pp.1647-1651, 1996.
DOI : 10.1002/eji.1830260736

H. Ahn, S. Maruo, M. Tomura, J. Mu, T. Hamaoka et al., A mechanism underlying synergy between IL-12 and IFN-gamma-inducing factor in enhanced production of IFN-gamma, J Immunol, vol.159, pp.2125-2131, 1997.

J. Gracie, R. Forsey, W. Chan, A. Gilmour, B. Leung et al., A proinflammatory role for IL-18 in rheumatoid arthritis, Journal of Clinical Investigation, vol.104, issue.10, pp.1393-1401, 1999.
DOI : 10.1172/JCI7317

M. Yamamura, M. Kawashima, M. Taniai, H. Yamauchi, T. Tanimoto et al., Interferon-?-inducing activity of interleukin-18 in the joint with rheumatoid arthritis, Arthritis & Rheumatism, vol.185, issue.2, pp.275-285, 2001.
DOI : 10.1002/1529-0131(200102)44:2<275::AID-ANR44>3.0.CO;2-B

Y. Aizawa, K. Akita, M. Taniai, K. Torigoe, T. Mori et al., Cloning and expression of interleukin-18 binding protein, FEBS Letters, vol.209, issue.2-3, pp.338-342, 1999.
DOI : 10.1016/S0014-5793(99)00148-9

D. Novick, S. Kim, G. Fantuzzi, L. Reznikov, C. Dinarello et al., Interleukin-18 Binding Protein, Immunity, vol.10, issue.1, pp.127-136, 1999.
DOI : 10.1016/S1074-7613(00)80013-8

URL : http://doi.org/10.1016/s1074-7613(00)80013-8

F. Arnett, S. Edworthy, D. Bloch, D. Mcshane, J. Fries et al., The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis, Arthritis & Rheumatism, vol.143, issue.3, pp.315-324, 1988.
DOI : 10.1002/art.1780310302

T. Germann, J. Szeliga, H. Hess, S. Storkel, F. Podlaski et al., Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice., Proceedings of the National Academy of Sciences, vol.92, issue.11, pp.4823-4827, 1995.
DOI : 10.1073/pnas.92.11.4823

S. Trembleau, G. Penna, E. Bosi, A. Mortara, M. Gately et al., Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice, Journal of Experimental Medicine, vol.181, issue.2, pp.817-821, 1995.
DOI : 10.1084/jem.181.2.817

J. Leonard, K. Waldburger, and S. Goldman, Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12, Journal of Experimental Medicine, vol.181, issue.1, pp.381-386, 1995.
DOI : 10.1084/jem.181.1.381

M. Neurath, I. Fuss, B. Kelsall, E. Stuber, and W. Strober, Antibodies to interleukin 12 abrogate established experimental colitis in mice, Journal of Experimental Medicine, vol.182, issue.5, pp.1281-1290, 1995.
DOI : 10.1084/jem.182.5.1281

Y. Yanagihara, K. Shiozawa, M. Takai, M. Kyogoku, and S. Shiozawa, Natural killer (NK) T cells are significantly decreased in the peripheral blood of patients with rheumatoid arthritis (RA), Clinical & Experimental Immunology, vol.11, issue.1
DOI : 10.1084/jem.173.4.869

A. Maldonado, Y. Mueller, P. Thomas, P. Bojczuk, O. Connors et al., Decreased effector memory CD45RA+ CD62L- CD8+ T cells and increased central memory CD45RA- CD62L+ CD8+ T cells in peripheral blood of rheumatoid arthritis patients, Arthritis Research & Therapy, vol.5, issue.2, pp.91-96, 2003.
DOI : 10.1186/ar619

K. Ezawa, M. Yamamura, H. Matsui, Z. Ota, and H. Makino, Comparative analysis of CD45RA-and CD45RO-positive CD4+T cells in peripheral blood, synovial fluid, and synovial tissue in patients with rheumatoid arthritis and osteoarthritis, Acta Med Okayama, vol.51, pp.25-31, 1997.

L. Rink, I. Cakman, and H. Kirchner, Altered cytokine production in the elderly, Mechanisms of Ageing and Development, vol.102, issue.2-3, pp.199-209, 1998.
DOI : 10.1016/S0047-6374(97)00153-X

A. Haddad, J. Bienvenu, and P. Miossec, Increased production of a Th2 cytokine profile by activated whole blood cells from rheumatoid arthritis patients, Journal of Clinical Immunology, vol.18, issue.6, pp.399-403, 1998.
DOI : 10.1023/A:1023278606036

M. Maurice, W. Van-der-graaff, A. Leow, F. Breedveld, R. Van-lier et al., Treatment with monoclonal anti-tumor necrosis factor ? antibody results in an accumulation of Th1 CD4+ T cells in the peripheral blood of patients with rheumatoid arthritis, Arthritis & Rheumatism, vol.173, issue.10, pp.2166-2173, 1999.
DOI : 10.1002/1529-0131(199910)42:10<2166::AID-ANR18>3.0.CO;2-K

F. Austrup, D. Vestweber, E. Borges, M. Lohning, R. Brauer et al., P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues, Nature, vol.385, issue.6611, pp.81-83, 1997.
DOI : 10.1038/385081a0

P. Tak, P. Taylor, F. Breedveld, T. Smeets, M. Daha et al., Decrease in cellularity and expression of adhesion molecules by anti???tumor necrosis factor ?? monoclonal antibody treatment in patients with rheumatoid arthritis, Arthritis & Rheumatism, vol.97, issue.7, pp.1077-1081, 1996.
DOI : 10.1002/art.1780390702

J. Keane, G. S. Wise, R. Mirabile-levens, E. Kasznica, J. Schwieterman et al., Tuberculosis Associated with Infliximab, a Tumor Necrosis Factor ?????Neutralizing Agent, New England Journal of Medicine, vol.345, issue.15, pp.1098-1104, 2001.
DOI : 10.1056/NEJMoa011110

M. Prof-pierre, Arsonval, Department of Immunology and Rheumatology and INSERM U-403, Pavillon F, Hospital Edouard Herriot Tel: +33 472 117487; fax: +33 472 117429; e-mail pierre.miossec@univ-lyon1.fr Available online http