• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of immunologyLink to Publisher's site
Immunology. Sep 1993; 80(1): 96–102.
PMCID: PMC1422109

Expression and function of CD5 and CD28 in patients with rheumatoid arthritis.


To assess the role of CD5 and CD28 in the pathogenesis of the decreased cellular immune function in patients with rheumatoid arthritis (RA) we analysed the expression and function of these T-cell surface molecules. The expression of CD5 as well as of CD28 in synovial and peripheral blood T cells was similar to that of control T cells. Monoclonal antibodies (mAb) directed at CD28 and CD5 were able to provide an accessory signal to anti-CD3 activated T cells both from the synovial fluid and from the peripheral blood. However, the proliferation induced by anti-CD3 mAb in conjunction with anti-CD5 or anti-CD28 mAb was always higher in peripheral blood (PB) T cells compared to the paired synovial fluid T cells. After simultaneous ligation of CD5 and CD28, proliferation was induced in the PB T cells. However, when compared to control PB T cells, this proliferation was significantly lower in the RA patients. Purified normal memory (CD45RO+) T cells proliferated less strongly than naive (CD45RA+) T cells, but no difference was observed between rheumatoid and normal memory T-cell proliferative responses. However, enriched PB CD45RA+ T cells from rheumatoid patients proliferated less vigorously to CD5 and CD28 ligation when compared to normal enriched CD45RA+ T cells. Synovial fluid (SF) T cells, which are mainly of the memory cell type, did not proliferate after simultaneous ligation of CD5 and CD28. This refractory state of synovial T cells could not be explained by a difference in the surface expression of CD5 or CD28. Our data suggest that the cellular immune dysfunction in the PB from rheumatoid patients may be due to a decreased responsiveness of the naive T-cell subset to accessory signals provided by CD5 and CD28. In addition, SF T cells appear hyporesponsive to stimulating signals provided through CD5 and CD28.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Haraoui B, Wilder RL, Malone DG, Allen JB, Katona IM, Wahl SM. Immune function in severe, active rheumatoid arthritis: a relationship between peripheral blood mononuclear cell proliferation to soluble antigens and mononuclear cell subset profiles. J Immunol. 1984 Aug;133(2):697–701. [PubMed]
  • Verwilghen J, Vertessen S, Stevens EA, Dequeker J, Ceuppens JL. Depressed T-cell reactivity to recall antigens in rheumatoid arthritis. J Clin Immunol. 1990 Mar;10(2):90–98. [PubMed]
  • Silverman HA, Johnson JS, Vaughan JH, McGlamory JC. Altered lymphocyte reactivity in rheumatoid arthritis. Arthritis Rheum. 1976 May-Jun;19(3):509–515. [PubMed]
  • Keystone EC, Poplonski L, Miller RG, Gorczynski R, Gladman D, Snow K. Reactivity of T-cells from patients with rheumatoid arthritis to anti-CD3 antibody. Clin Immunol Immunopathol. 1988 Sep;48(3):325–337. [PubMed]
  • Pope RM, McChesney L, Talal N, Fischbach M. Characterization of the defective autologous mixed lymphocyte response in rheumatoid arthritis. Arthritis Rheum. 1984 Nov;27(11):1234–1244. [PubMed]
  • Corrigall V, Panayi GS, Laurent R. Lymphocyte studies in rheumatoid arthritis. III. A comparative study of the responses of peripheral blood and synovial fluid lymphocytes to phytomitogens. Scand J Rheumatol. 1979;8(1):10–16. [PubMed]
  • Burmester GR, Kalden JR, Peter HH, Schedel I, Beck P, Wittenborg A. Immunological and functional characteristics of peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis. Scand J Immunol. 1978;7(5):405–417. [PubMed]
  • Panayi GS. Response of rheumatoid-synovial-fluid lymphocytes to non-specific mitogens. Lancet. 1973 Sep 1;2(7827):512–513. [PubMed]
  • Abrahamsen TG, Frøland SS, Natvig JB. In vitro mitogen stimulation of synovial fluid lymphocytes from rheumatoid arthritis and juvenile rheumatoid arthritis patients: dissociation between the response to antigens and polyclonal mitogens. Scand J Immunol. 1978;7(1):81–90. [PubMed]
  • Jahn B, Burmester GR, Stock P, Rohwer P, Kalden JR. Functional and phenotypical characterization of activated T cells from intra-articular sites in inflammatory joint diseases. Possible modulation of the CD3 antigen. Scand J Immunol. 1987 Dec;26(6):745–754. [PubMed]
  • Talal N, Tovar Z, Dauphinee MJ, Flescher E, Dang H, Galarza D. Abnormalities of T cell activation in the rheumatoid synovium detected with monoclonal antibodies to CD3. Scand J Rheumatol Suppl. 1988;76:175–182. [PubMed]
  • Klareskog L, Forsum U, Scheynius A, Kabelitz D, Wigzell H. Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3632–3636. [PMC free article] [PubMed]
  • Janossy G, Panayi G, Duke O, Bofill M, Poulter LW, Goldstein G. Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. Lancet. 1981 Oct 17;2(8251):839–842. [PubMed]
  • Schwartz RH. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. [PubMed]
  • Springer TA. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. [PubMed]
  • DeFranco AL. Between B cells and T cells. Nature. 1991 Jun 20;351(6328):603–604. [PubMed]
  • Ceuppens JL, Baroja ML. Monoclonal antibodies to the CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase-bound OKT3. J Immunol. 1986 Sep 15;137(6):1816–1821. [PubMed]
  • Hara T, Fu SM, Hansen JA. Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). J Exp Med. 1985 Jun 1;161(6):1513–1524. [PMC free article] [PubMed]
  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [PubMed]
  • Verwilghen J, Baroja ML, Van Vaeck F, Van Damme J, Ceuppens JL. Differences in the stimulating capacity of immobilized anti-CD3 monoclonal antibodies: variable dependence on interleukin-1 as a helper signal for T-cell activation. Immunology. 1991 Feb;72(2):269–276. [PMC free article] [PubMed]
  • Verwilghen J, Vandenberghe P, Wallays G, de Boer M, Anthony N, Panayi GS, Ceuppens JL. Simultaneous ligation of CD5 and CD28 on resting T lymphocytes induces T cell activation in the absence of T cell receptor/CD3 occupancy. J Immunol. 1993 Feb 1;150(3):835–846. [PubMed]
  • Wolinsky SI, Goodwin JS, Messner RP, Williams RC., Jr Role of prostaglandin in the depressed cell-mediated immune response in rheumatoid arthritis. Clin Immunol Immunopathol. 1980 Sep;17(1):31–37. [PubMed]
  • Seitz M, Napierski I, Kirchner H. Depressed PPD and tetanus toxoid presentation by monocytes to T lymphocytes in patients with rheumatoid arthritis: restoration by interferon gamma. Rheumatol Int. 1988;8(5):189–196. [PubMed]
  • Ledbetter JA, June CH, Grosmaire LS, Rabinovitch PS. Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1384–1388. [PMC free article] [PubMed]
  • Lotz M, Tsoukas CD, Robinson CA, Dinarello CA, Carson DA, Vaughan JH. Basis for defective responses of rheumatoid arthritis synovial fluid lymphocytes to anti-CD3 (T3) antibodies. J Clin Invest. 1986 Sep;78(3):713–721. [PMC free article] [PubMed]
  • Emery P, Gentry KC, Kelso A, Mackay IR. Interleukin 2 inhibitor in synovial fluid. Clin Exp Immunol. 1988 Apr;72(1):60–66. [PMC free article] [PubMed]
  • Hovdenes J, Gaudernack G, Kvien TK, Egeland T, Mellbye OJ. A functional study of purified CD4+ and CD8+ cells isolated from synovial fluid of patients with rheumatoid arthritis and other arthritides. Scand J Immunol. 1989 Jun;29(6):641–649. [PubMed]
  • Linardopoulos S, Corrigall V, Panayi GS. Activation of HLA-DR and interleukin-6 gene transcription in resting T cells via the CD2 molecule: relevance to chronic immune-mediated inflammation. Scand J Immunol. 1992 Sep;36(3):469–477. [PubMed]
  • 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. [PubMed]
  • Lasky HP, Bauer K, Pope RM. Increased helper inducer and decreased suppressor inducer phenotypes in the rheumatoid joint. Arthritis Rheum. 1988 Jan;31(1):52–59. [PubMed]
  • Verwilghen J, Kingsley GH, Ceuppens JL, Panayi GS. Inhibition of synovial fluid T cell proliferation by anti-CD5 monoclonal antibodies. A potential mechanism for their immunotherapeutic action in vivo. Arthritis Rheum. 1992 Dec;35(12):1445–1451. [PubMed]

Articles from Immunology are provided here courtesy of British Society for Immunology


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

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...