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. 1991 Feb;72(2):250–255.

An investigation of T-cell subset phenotype and function in the rheumatoid synovium using in situ hybridization for IL-2 mRNA.

C J Warren 1, W M Howell 1, M Bhambhani 1, M I Cawley 1, J L Smith 1
PMCID: PMC1384492  PMID: 2016122

Abstract

Cryostat sections of synovial biopsy tissue from patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA) have been investigated for interleukin-2 (IL-2) mRNA and protein production. In situ hybridization using 32P-labelled oligonucleotide probes based on IL-2 gene sequences coded by exon 1 and exon 3 of the IL-2 gene revealed IL-2 mRNA over lymphoid aggregates in RA and SpA tissue. No IL-2 mRNA was detected in OA tissue and reflected the absence of lymphoid infiltrates in these tissues. Total mRNA, as detected by a 32P oligo dT probe, was found in all tissue examined. IL-2 protein product was detected by monoclonal antibody staining in SpA but not in RA or OA tissue. This is the first report of in situ studies of lymphoid function in the microenvironment of the RA synovium. Whether these data reflect the function of normal CD3+ CD4+ CD45RO+ T-cell subsets in the diseased joint remains to be resolved.

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Selected References

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  1. Bettens F., Walker C., Gauchat J. F., Gauchat D., Wyss T., Pichler W. J. Lymphokine gene expression related to CD4 T cell subset (CD45R/CDw29) phenotype conversion. Eur J Immunol. 1989 Sep;19(9):1569–1574. doi: 10.1002/eji.1830190908. [DOI] [PubMed] [Google Scholar]
  2. Bottomly K. A functional dichotomy in CD4+ T lymphocytes. Immunol Today. 1988 Sep;9(9):268–274. doi: 10.1016/0167-5699(88)91308-4. [DOI] [PubMed] [Google Scholar]
  3. Buchan G., Barrett K., Fujita T., Taniguchi T., Maini R., Feldmann M. Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interleukin-2 (IL-2) IL-2 receptor and IFN-gamma. Clin Exp Immunol. 1988 Feb;71(2):295–301. [PMC free article] [PubMed] [Google Scholar]
  4. Combe B., Pope R. M., Fischbach M., Darnell B., Baron S., Talal N. Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood. Clin Exp Immunol. 1985 Mar;59(3):520–528. [PMC free article] [PubMed] [Google Scholar]
  5. Dohlsten M., Hedlund G., Sjögren H. O., Carlsson R. Two subsets of human CD4+ T helper cells differing in kinetics and capacities to produce interleukin 2 and interferon-gamma can be defined by the Leu-18 and UCHL1 monoclonal antibodies. Eur J Immunol. 1988 Aug;18(8):1173–1178. doi: 10.1002/eji.1830180805. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Feldmann M., Brennan F. M., Chantry D., Haworth C., Turner M., Abney E., Buchan G., Barrett K., Barkley D., Chu A. Cytokine production in the rheumatoid joint: implications for treatment. Ann Rheum Dis. 1990 Jun;49 (Suppl 1):480–486. [PubMed] [Google Scholar]
  8. 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]
  9. Holbrook N. J., Smith K. A., Fornace A. J., Jr, Comeau C. M., Wiskocil R. L., Crabtree G. R. T-cell growth factor: complete nucleotide sequence and organization of the gene in normal and malignant cells. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1634–1638. doi: 10.1073/pnas.81.6.1634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Howley P. M., Israel M. A., Law M. F., Martin M. A. A rapid method for detecting and mapping homology between heterologous DNAs. Evaluation of polyomavirus genomes. J Biol Chem. 1979 Jun 10;254(11):4876–4883. [PubMed] [Google Scholar]
  11. Husby G., Williams R. C., Jr Immunohistochemical studies of interleukin-2 and gamma-interferon in rheumatoid arthritis. Arthritis Rheum. 1985 Feb;28(2):174–181. doi: 10.1002/art.1780280212. [DOI] [PubMed] [Google Scholar]
  12. Kidd B. L., Moore K., Walters M. T., Smith J. L., Cawley M. I. Immunohistological features of synovitis in ankylosing spondylitis: a comparison with rheumatoid arthritis. Ann Rheum Dis. 1989 Feb;48(2):92–98. doi: 10.1136/ard.48.2.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kitas G. D., Salmon M., Farr M., Gaston J. S., Bacon P. A. Deficient interleukin 2 production in rheumatoid arthritis: association with active disease and systemic complications. Clin Exp Immunol. 1988 Aug;73(2):242–249. [PMC free article] [PubMed] [Google Scholar]
  14. Lemm G., Warnatz H. Evidence for enhanced interleukin 2 (IL-2) secretion and IL-2 receptor presentation by synovial fluid lymphocytes in rheumatoid arthritis. Clin Exp Immunol. 1986 Apr;64(1):71–79. [PMC free article] [PubMed] [Google Scholar]
  15. Miossec P., Kashiwado T., Ziff M. Inhibitor of interleukin-2 in rheumatoid synovial fluid. Arthritis Rheum. 1987 Feb;30(2):121–129. doi: 10.1002/art.1780300201. [DOI] [PubMed] [Google Scholar]
  16. Moore K., Walters M. T., Jones D. B., Garvey E., Harvey J., Cawley M. I., Smith J. L. An immunohistological study of CD4+ lymphocyte subsets within inflammatory lesions with special reference to rheumatoid arthritis and inflammatory bowel disease. Immunology. 1988 Nov;65(3):457–463. [PMC free article] [PubMed] [Google Scholar]
  17. Nesbitt A. M., Jones D. B., Moore K. Phenotypic changes in a CD4+ lymphocyte subset correlate with a conversion from suppressor to helper inducer function. Immunology. 1990 Jan;69(1):65–70. [PMC free article] [PubMed] [Google Scholar]
  18. Powrie F., Mason D. Phenotypic and functional heterogeneity of CD4+ T cells. Immunol Today. 1988 Sep;9(9):274–277. doi: 10.1016/0167-5699(88)91309-6. [DOI] [PubMed] [Google Scholar]
  19. Rentrop M., Knapp B., Winter H., Schweizer J. Aminoalkylsilane-treated glass slides as support for in situ hybridization of keratin cDNAs to frozen tissue sections under varying fixation and pretreatment conditions. Histochem J. 1986 May;18(5):271–276. doi: 10.1007/BF01676237. [DOI] [PubMed] [Google Scholar]
  20. Salmon M., Kitas G. D., Emery P. Another interpretation of the role of T helper cells in the rheumatoid synovium. Arthritis Rheum. 1989 Jun;32(6):795–796. doi: 10.1002/anr.1780320621. [DOI] [PubMed] [Google Scholar]
  21. Smith M. D., Roberts-Thomson P. J. Interleukin 2 and interleukin 2 inhibitors in human serum and synovial fluid. II. Mitogenic stimulation, interleukin 2 production and interleukin 2 receptor expression in rheumatoid arthritis, psoriatic arthritis and Reiter's syndrome. J Rheumatol. 1989 Jul;16(7):897–903. [PubMed] [Google Scholar]
  22. Wallace D. L., Beverley P. C. Phenotypic changes associated with activation of CD45RA+ and CD45RO+ T cells. Immunology. 1990 Mar;69(3):460–467. [PMC free article] [PubMed] [Google Scholar]
  23. Walters M. T., Smith J. L., Moore K., Evans P. R., Cawley M. I. An investigation of the action of disease modifying antirheumatic drugs on the rheumatoid synovial membrane: reduction in T lymphocyte subpopulations and HLA-DP and DQ antigen expression after gold or penicillamine therapy. Ann Rheum Dis. 1987 Jan;46(1):7–16. doi: 10.1136/ard.46.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]

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