Altered T lymphocyte signaling in rheumatoid arthritis

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Colleges, School and Institutes

Abstract

Synovial and peripheral blood T cells from patients with rheumatoid arthritis are functionally deficient. This may be secondary to their reduced cytokine (e.g. interleukin-2) synthesis. We have investigated the possibility of an alteration in pathways common to interleukin-2 production and proliferation in peripheral blood T cells from patients with active rheumatoid arthritis. Intracellular calcium levels ([Ca2+]i) were analyzed by flow cytometric methods in Indo1-loaded T cells. These were purified by negative selection from patients or age/sex-matched controls, and stimulated with phytohemagglutinin-P or anti-CD3. Rheumatoid [Ca2+]i responses to both stimuli were reduced (p <0.005). Patient cell samples included a larger proportion of non-responding cells, but even in the responsive population the magnitude of the response in rheumatoid cells was impaired compared with those in normal cell samples (p <0.0001) for both stimuli. Proliferation responses were also impaired (p <0.005), and there was a positive correlation between the paired [Ca2+]i elevation and proliferative responses for both stimuli. CD2 and CD3 expression were normal, and the proportions of CD4, CD8 and CD45RO and CD45RA subsets were also unaffected by disease. Thus a signaling defect downstream of CD2 or CD3 surface molecules may contribute to functional deficiencies in rheumatoid T lymphocytes. This effect is not due to non-steroidal anti-inflammatory drugs which some patients were taking. We have demonstrated similar alterations in [Ca2+]i responses and proliferation in a smaller study of patients with inflammatory bowel disease, indicating that such changes might be present in other chronic inflammatory states.

Details

Original languageEnglish
Pages (from-to)1547-54
Number of pages8
JournalEuropean Journal of Immunology
Volume25
Issue number6
Publication statusPublished - Jun 1995

Keywords

  • Calcium, Interleukin-2, Humans, Antigens, CD, Arthritis, Rheumatoid, Flow Cytometry, Signal Transduction, Male, Female, T-Lymphocytes, Cell Division