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. 1997 Nov 1;100(9):2404–2414. doi: 10.1172/JCI119781

Functional CD40 ligand is expressed by T cells in rheumatoid arthritis.

K P MacDonald 1, Y Nishioka 1, P E Lipsky 1, R Thomas 1
PMCID: PMC508439  PMID: 9410920

Abstract

CD40 ligand (CD40-L), a member of the tumor necrosis family of transmembrane glycoproteins, is rapidly and transiently expressed on the surface of recently activated CD4+ T cells. Interactions between CD40-L and CD40 induce B cell immunoglobulin production as well as monocyte activation and dendritic cell differentiation. Since these features characterize rheumatoid arthritis (RA), the expression and function of CD40-L in RA was examined. Freshly isolated RA peripheral blood (PB) and synovial fluid (SF) T cells expressed CD40-L mRNA as well as low level cell surface CD40-L. An additional subset of CD4+ RA SF T cells upregulated cell surface CD40-L expression within 15 min of in vitro activation even in the presence of cycloheximide, but soluble CD40-L was not found in SF. CD40-L expressed by RA T cells was functional, since RA PB and SF T cells but not normal PB T cells stimulated CD40-L-dependent B cell immunoglobulin production and dendritic cell IL-12 expression in the absence of prolonged in vitro T cell activation. In view of the diverse proinflammatory effects of CD40-L, this molecule is likely to play a central role in the perpetuation of rheumatoid synovitis. Of importance, blockade of CD40-L may prove highly effective as a disease modifying therapy for RA.

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Selected References

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  1. Aaron S., Paetkau V. Synovial cell secretion of IL-2 in vitro, a limiting dilution analysis. Clin Exp Rheumatol. 1991 Mar-Apr;9(2):113–118. [PubMed] [Google Scholar]
  2. Alderson M. R., Armitage R. J., Tough T. W., Strockbine L., Fanslow W. C., Spriggs M. K. CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40. J Exp Med. 1993 Aug 1;178(2):669–674. doi: 10.1084/jem.178.2.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  4. Burmester G. R., Emmrich F. Anti-CD4 therapy in rheumatoid arthritis. Clin Exp Rheumatol. 1993 Mar-Apr;11 (Suppl 8):S139–S145. [PubMed] [Google Scholar]
  5. Calin A., Elswood J., Klouda P. T. Destructive arthritis, rheumatoid factor, and HLA-DR4. Susceptibility versus severity, a case-control study. Arthritis Rheum. 1989 Oct;32(10):1221–1225. doi: 10.1002/anr.1780321006. [DOI] [PubMed] [Google Scholar]
  6. Casamayor-Palleja M., Khan M., MacLennan I. C. A subset of CD4+ memory T cells contains preformed CD40 ligand that is rapidly but transiently expressed on their surface after activation through the T cell receptor complex. J Exp Med. 1995 Apr 1;181(4):1293–1301. doi: 10.1084/jem.181.4.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Castle B. E., Kishimoto K., Stearns C., Brown M. L., Kehry M. R. Regulation of expression of the ligand for CD40 on T helper lymphocytes. J Immunol. 1993 Aug 15;151(4):1777–1788. [PubMed] [Google Scholar]
  8. Caux C., Massacrier C., Vanbervliet B., Dubois B., Van Kooten C., Durand I., Banchereau J. Activation of human dendritic cells through CD40 cross-linking. J Exp Med. 1994 Oct 1;180(4):1263–1272. doi: 10.1084/jem.180.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cella M., Scheidegger D., Palmer-Lehmann K., Lane P., Lanzavecchia A., Alber G. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med. 1996 Aug 1;184(2):747–752. doi: 10.1084/jem.184.2.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chen E., Keystone E. C., Fish E. N. Restricted cytokine expression in rheumatoid arthritis. Arthritis Rheum. 1993 Jul;36(7):901–910. doi: 10.1002/art.1780360706. [DOI] [PubMed] [Google Scholar]
  11. Cush J. J., Lipsky P. E. Phenotypic analysis of synovial tissue and peripheral blood lymphocytes isolated from patients with rheumatoid arthritis. Arthritis Rheum. 1988 Oct;31(10):1230–1238. doi: 10.1002/art.1780311003. [DOI] [PubMed] [Google Scholar]
  12. Desai-Mehta A., Lu L., Ramsey-Goldman R., Datta S. K. Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production. J Clin Invest. 1996 May 1;97(9):2063–2073. doi: 10.1172/JCI118643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dolhain R. J., ter Haar N. T., Hoefakker S., Tak P. P., de Ley M., Claassen E., Breedveld F. C., Miltenburg A. M. Increased expression of interferon (IFN)-gamma together with IFN-gamma receptor in the rheumatoid synovial membrane compared with synovium of patients with osteoarthritis. Br J Rheumatol. 1996 Jan;35(1):24–32. doi: 10.1093/rheumatology/35.1.24. [DOI] [PubMed] [Google Scholar]
  14. Durie F. H., Fava R. A., Foy T. M., Aruffo A., Ledbetter J. A., Noelle R. J. Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. Science. 1993 Sep 3;261(5126):1328–1330. doi: 10.1126/science.7689748. [DOI] [PubMed] [Google Scholar]
  15. Durie F. H., Foy T. M., Masters S. R., Laman J. D., Noelle R. J. The role of CD40 in the regulation of humoral and cell-mediated immunity. Immunol Today. 1994 Sep;15(9):406–411. doi: 10.1016/0167-5699(94)90269-0. [DOI] [PubMed] [Google Scholar]
  16. Elliott M. J., Maini R. N., Feldmann M., Long-Fox A., Charles P., Katsikis P., Brennan F. M., Walker J., Bijl H., Ghrayeb J. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum. 1993 Dec;36(12):1681–1690. doi: 10.1002/art.1780361206. [DOI] [PubMed] [Google Scholar]
  17. Emery P., Gentry K. C., Mackay I. R., Muirden K. D., Rowley M. Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis. Arthritis Rheum. 1987 Aug;30(8):849–856. doi: 10.1002/art.1780300802. [DOI] [PubMed] [Google Scholar]
  18. Fanslow W. C., Srinivasan S., Paxton R., Gibson M. G., Spriggs M. K., Armitage R. J. Structural characteristics of CD40 ligand that determine biological function. Semin Immunol. 1994 Oct;6(5):267–278. doi: 10.1006/smim.1994.1035. [DOI] [PubMed] [Google Scholar]
  19. Firestein G. S., Zvaifler N. J. How important are T cells in chronic rheumatoid synovitis? Arthritis Rheum. 1990 Jun;33(6):768–773. doi: 10.1002/art.1780330602. [DOI] [PubMed] [Google Scholar]
  20. Fox R. I., Fong S., Sabharwal N., Carstens S. A., Kung P. C., Vaughan J. H. Synovial fluid lymphocytes differ from peripheral blood lymphocytes in patients with rheumatoid arthritis. J Immunol. 1982 Jan;128(1):351–354. [PubMed] [Google Scholar]
  21. Gerritse K., Laman J. D., Noelle R. J., Aruffo A., Ledbetter J. A., Boersma W. J., Claassen E. CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2499–2504. doi: 10.1073/pnas.93.6.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Graf D., Müller S., Korthäuer U., van Kooten C., Weise C., Kroczek R. A. A soluble form of TRAP (CD40 ligand) is rapidly released after T cell activation. Eur J Immunol. 1995 Jun;25(6):1749–1754. doi: 10.1002/eji.1830250639. [DOI] [PubMed] [Google Scholar]
  23. Grammer A. C., Bergman M. C., Miura Y., Fujita K., Davis L. S., Lipsky P. E. The CD40 ligand expressed by human B cells costimulates B cell responses. J Immunol. 1995 May 15;154(10):4996–5010. [PubMed] [Google Scholar]
  24. Hahn G., Stuhlmüller B., Hain N., Kalden J. R., Pfizenmaier K., Burmester G. R. Modulation of monocyte activation in patients with rheumatoid arthritis by leukapheresis therapy. J Clin Invest. 1993 Mar;91(3):862–870. doi: 10.1172/JCI116307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hollenbaugh D., Grosmaire L. S., Kullas C. D., Chalupny N. J., Braesch-Andersen S., Noelle R. J., Stamenkovic I., Ledbetter J. A., Aruffo A. The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. EMBO J. 1992 Dec;11(12):4313–4321. doi: 10.1002/j.1460-2075.1992.tb05530.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hollenbaugh D., Wu L. H., Ochs H. D., Nonoyama S., Grosmaire L. S., Ledbetter J. A., Noelle R. J., Hill H., Aruffo A. The random inactivation of the X chromosome carrying the defective gene responsible for X-linked hyper IgM syndrome (X-HIM) in female carriers of HIGM1. J Clin Invest. 1994 Aug;94(2):616–622. doi: 10.1172/JCI117377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Horgan K. J., Tanaka Y., Luce G. E., van Seventer G. A., Nutman T. B., Shaw S. CD45RB expression defines two interconvertible subsets of human CD4+ T cells with memory function. Eur J Immunol. 1994 May;24(5):1240–1243. doi: 10.1002/eji.1830240536. [DOI] [PubMed] [Google Scholar]
  28. Howell M., Smith J., Cawley M. The rheumatoid synovium: a model for T-cell anergy? Immunol Today. 1992 May;13(5):191–191. doi: 10.1016/0167-5699(92)90127-S. [DOI] [PubMed] [Google Scholar]
  29. Hoxie J. A., Matthews D. M., Callahan K. J., Cassel D. L., Cooper R. A. Transient modulation and internalization of T4 antigen induced by phorbol esters. J Immunol. 1986 Aug 15;137(4):1194–1201. [PubMed] [Google Scholar]
  30. Kiener P. A., Moran-Davis P., Rankin B. M., Wahl A. F., Aruffo A., Hollenbaugh D. Stimulation of CD40 with purified soluble gp39 induces proinflammatory responses in human monocytes. J Immunol. 1995 Nov 15;155(10):4917–4925. [PubMed] [Google Scholar]
  31. Kitas G. D., Salmon M., Allan I. M., Bacon P. A. The T cell system in rheumatoid arthritis: activated or defective? Scand J Rheumatol Suppl. 1988;76:161–173. doi: 10.3109/03009748809102966. [DOI] [PubMed] [Google Scholar]
  32. Koch A. E., Kunkel S. L., Harlow L. A., Johnson B., Evanoff H. L., Haines G. K., Burdick M. D., Pope R. M., Strieter R. M. Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. J Clin Invest. 1992 Sep;90(3):772–779. doi: 10.1172/JCI115950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kohem C. L., Brezinschek R. I., Wisbey H., Tortorella C., Lipsky P. E., Oppenheimer-Marks N. Enrichment of differentiated CD45RBdim,CD27- memory T cells in the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum. 1996 May;39(5):844–854. doi: 10.1002/art.1780390518. [DOI] [PubMed] [Google Scholar]
  34. Kroczek R. A., Graf D., Brugnoni D., Giliani S., Korthüer U., Ugazio A., Senger G., Mages H. W., Villa A., Notarangelo L. D. Defective expression of CD40 ligand on T cells causes "X-linked immunodeficiency with hyper-IgM (HIGM1)". Immunol Rev. 1994 Apr;138:39–59. doi: 10.1111/j.1600-065x.1994.tb00846.x. [DOI] [PubMed] [Google Scholar]
  35. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  36. Larsen C. P., Elwood E. T., Alexander D. Z., Ritchie S. C., Hendrix R., Tucker-Burden C., Cho H. R., Aruffo A., Hollenbaugh D., Linsley P. S. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature. 1996 May 30;381(6581):434–438. doi: 10.1038/381434a0. [DOI] [PubMed] [Google Scholar]
  37. Ludewig B., Graf D., Gelderblom H. R., Becker Y., Kroczek R. A., Pauli G. Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40-ligand) and TNF-alpha, but strongly enhanced by interleukin-10. Eur J Immunol. 1995 Jul;25(7):1943–1950. doi: 10.1002/eji.1830250722. [DOI] [PubMed] [Google Scholar]
  38. Mach F., Schönbeck U., Sukhova G. K., Bourcier T., Bonnefoy J. Y., Pober J. S., Libby P. Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1931–1936. doi: 10.1073/pnas.94.5.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Maini R. N., Elliott M. J., Brennan F. M., Williams R. O., Chu C. Q., Paleolog E., Charles P. J., Taylor P. C., Feldmann M. Monoclonal anti-TNF alpha antibody as a probe of pathogenesis and therapy of rheumatoid disease. Immunol Rev. 1995 Apr;144:195–223. doi: 10.1111/j.1600-065x.1995.tb00070.x. [DOI] [PubMed] [Google Scholar]
  40. Mason D., Powrie F. Memory CD4+ T cells in man form two distinct subpopulations, defined by their expression of isoforms of the leucocyte common antigen, CD45. Immunology. 1990 Aug;70(4):427–433. [PMC free article] [PubMed] [Google Scholar]
  41. Matthews N., Emery P., Pilling D., Akbar A., Salmon M. Subpopulations of primed T helper cells in rheumatoid arthritis. Arthritis Rheum. 1993 May;36(5):603–607. doi: 10.1002/art.1780360505. [DOI] [PubMed] [Google Scholar]
  42. Mazzei G. J., Edgerton M. D., Losberger C., Lecoanet-Henchoz S., Graber P., Durandy A., Gauchat J. F., Bernard A., Allet B., Bonnefoy J. Y. Recombinant soluble trimeric CD40 ligand is biologically active. J Biol Chem. 1995 Mar 31;270(13):7025–7028. doi: 10.1074/jbc.270.13.7025. [DOI] [PubMed] [Google Scholar]
  43. Moreland L. W., Pratt P. W., Mayes M. D., Postlethwaite A., Weisman M. H., Schnitzer T., Lightfoot R., Calabrese L., Zelinger D. J., Woody J. N. Double-blind, placebo-controlled multicenter trial using chimeric monoclonal anti-CD4 antibody, cM-T412, in rheumatoid arthritis patients receiving concomitant methotrexate. Arthritis Rheum. 1995 Nov;38(11):1581–1588. doi: 10.1002/art.1780381109. [DOI] [PubMed] [Google Scholar]
  44. Morimoto C., Romain P. L., Fox D. A., Anderson P., DiMaggio M., Levine H., Schlossman S. F. Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases. Am J Med. 1988 May;84(5):817–825. doi: 10.1016/0002-9343(88)90058-7. [DOI] [PubMed] [Google Scholar]
  45. Mulherin D., Fitzgerald O., Bresnihan B. Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum. 1996 Jan;39(1):115–124. doi: 10.1002/art.1780390116. [DOI] [PubMed] [Google Scholar]
  46. Nishioka Y., Lipsky P. E. The role of CD40-CD40 ligand interaction in human T cell-B cell collaboration. J Immunol. 1994 Aug 1;153(3):1027–1036. [PubMed] [Google Scholar]
  47. Panayi G. S., Tugwell P. The use of cyclosporin A in rheumatoid arthritis: conclusions of an international review. Br J Rheumatol. 1994 Oct;33(10):967–969. doi: 10.1093/rheumatology/33.10.967. [DOI] [PubMed] [Google Scholar]
  48. Patel H. R., Oshiba A., Jeppson J. D., Gelfand E. W. Differential expression of CD40 ligand on T cell subsets. Implications for different roles of CD45RA+ and CD45RO+ cells in IgE production. J Immunol. 1996 Mar 1;156(5):1781–1787. [PubMed] [Google Scholar]
  49. Peitsch M. C., Tschopp J. Comparative molecular modelling of the Fas-ligand and other members of the TNF family. Mol Immunol. 1995 Jul;32(10):761–772. doi: 10.1016/0161-5890(95)00016-8. [DOI] [PubMed] [Google Scholar]
  50. Pitzalis C., Kingsley G., Haskard D., Panayi G. The preferential accumulation of helper-inducer T lymphocytes in inflammatory lesions: evidence for regulation by selective endothelial and homotypic adhesion. Eur J Immunol. 1988 Sep;18(9):1397–1404. doi: 10.1002/eji.1830180915. [DOI] [PubMed] [Google Scholar]
  51. Pitzalis C., Kingsley G., Lanchbury J. S., Murphy J., Panayi G. S. Expression of HLA-DR, DQ and DP antigens and interleukin-2 receptor on synovial fluid T lymphocyte subsets in rheumatoid arthritis: evidence for "frustrated" activation. J Rheumatol. 1987 Aug;14(4):662–666. [PubMed] [Google Scholar]
  52. Potocnik A. J., Kinne R., Menninger H., Zacher J., Emmrich F., Kroczek R. A. Expression of activation antigens on T cells in rheumatoid arthritis patients. Scand J Immunol. 1990 Feb;31(2):213–224. doi: 10.1111/j.1365-3083.1990.tb02762.x. [DOI] [PubMed] [Google Scholar]
  53. Rankin E. C., Choy E. H., Kassimos D., Kingsley G. H., Sopwith A. M., Isenberg D. A., Panayi G. S. The therapeutic effects of an engineered human anti-tumour necrosis factor alpha antibody (CDP571) in rheumatoid arthritis. Br J Rheumatol. 1995 Apr;34(4):334–342. doi: 10.1093/rheumatology/34.4.334. [DOI] [PubMed] [Google Scholar]
  54. Ridley M. G., Kingsley G., Pitzalis C., Panayi G. S. Monocyte activation in rheumatoid arthritis: evidence for in situ activation and differentiation in joints. Br J Rheumatol. 1990 Apr;29(2):84–88. doi: 10.1093/rheumatology/29.2.84. [DOI] [PubMed] [Google Scholar]
  55. Romani N., Gruner S., Brang D., Kämpgen E., Lenz A., Trockenbacher B., Konwalinka G., Fritsch P. O., Steinman R. M., Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994 Jul 1;180(1):83–93. doi: 10.1084/jem.180.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Schwartz R. H. Models of T cell anergy: is there a common molecular mechanism? J Exp Med. 1996 Jul 1;184(1):1–8. doi: 10.1084/jem.184.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Shimadzu M., Nunoi H., Terasaki H., Ninomiya R., Iwata M., Kanegasaka S., Matsuda I. Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome. Biochim Biophys Acta. 1995 Jan 2;1260(1):67–72. doi: 10.1016/0167-4781(94)00179-7. [DOI] [PubMed] [Google Scholar]
  58. Spriggs M. K., Fanslow W. C., Armitage R. J., Belmont J. The biology of the human ligand for CD40. J Clin Immunol. 1993 Nov;13(6):373–380. doi: 10.1007/BF00920012. [DOI] [PubMed] [Google Scholar]
  59. Tak P. P., van der Lubbe P. A., Cauli A., Daha M. R., Smeets T. J., Kluin P. M., Meinders A. E., Yanni G., Panayi G. S., Breedveld F. C. Reduction of synovial inflammation after anti-CD4 monoclonal antibody treatment in early rheumatoid arthritis. Arthritis Rheum. 1995 Oct;38(10):1457–1465. doi: 10.1002/art.1780381012. [DOI] [PubMed] [Google Scholar]
  60. Thiele D. L., Kurosaka M., Lipsky P. E. Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. J Immunol. 1983 Nov;131(5):2282–2290. [PubMed] [Google Scholar]
  61. Thiele D. L., Lipsky P. E. Modulation of human natural killer cell function by L-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol. 1985 Feb;134(2):786–793. [PubMed] [Google Scholar]
  62. Thomas R., Davis L. S., Lipsky P. E. Rheumatoid synovium is enriched in mature antigen-presenting dendritic cells. J Immunol. 1994 Mar 1;152(5):2613–2623. [PubMed] [Google Scholar]
  63. Thomas R., Lipsky P. E. Human peripheral blood dendritic cell subsets. Isolation and characterization of precursor and mature antigen-presenting cells. J Immunol. 1994 Nov 1;153(9):4016–4028. [PubMed] [Google Scholar]
  64. Thomas R., McIlraith M., Davis L. S., Lipsky P. E. Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation. Arthritis Rheum. 1992 Dec;35(12):1455–1465. doi: 10.1002/art.1780351209. [DOI] [PubMed] [Google Scholar]
  65. Thomas R., Quinn C. Functional differentiation of dendritic cells in rheumatoid arthritis: role of CD86 in the synovium. J Immunol. 1996 Apr 15;156(8):3074–3086. [PubMed] [Google Scholar]
  66. Tohma S., Lipsky P. E. Analysis of the mechanisms of T cell-dependent polyclonal activation of human B cells. Induction of human B cell responses by fixed activated T cells. J Immunol. 1991 Apr 15;146(8):2544–2552. [PubMed] [Google Scholar]
  67. Tortorella C., Schulze-Koops H., Thomas R., Splawski J. B., Davis L. S., Picker L. J., Lipsky P. E. Expression of CD45RB and CD27 identifies subsets of CD4+ memory T cells with different capacities to induce B cell differentiation. J Immunol. 1995 Jul 1;155(1):149–162. [PubMed] [Google Scholar]
  68. Wernick R. M., Lipsky P. E., Marban-Arcos E., Maliakkal J. J., Edelbaum D., Ziff M. IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures. Arthritis Rheum. 1985 Jul;28(7):742–752. doi: 10.1002/art.1780280704. [DOI] [PubMed] [Google Scholar]
  69. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Yellin M. J., Sippel K., Inghirami G., Covey L. R., Lee J. J., Sinning J., Clark E. A., Chess L., Lederman S. CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function. J Immunol. 1994 Jan 15;152(2):598–608. [PubMed] [Google Scholar]
  71. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. van Kooten C., Gaillard C., Galizzi J. P., Hermann P., Fossiez F., Banchereau J., Blanchard D. B cells regulate expression of CD40 ligand on activated T cells by lowering the mRNA level and through the release of soluble CD40. Eur J Immunol. 1994 Apr;24(4):787–792. doi: 10.1002/eji.1830240402. [DOI] [PubMed] [Google Scholar]
  73. van Zeben D., Hazes J. M., Zwinderman A. H., Vandenbroucke J. P., Breedveld F. C. Factors predicting outcome of rheumatoid arthritis: results of a followup study. J Rheumatol. 1993 Aug;20(8):1288–1296. [PubMed] [Google Scholar]

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