Rheumatoid synovium is enriched in CD45RBdim mature memory T cells that are potent helpers for B cell differentiation

Ranjeny Thomas, Melissa McIlraith, Laurie S. Davis, Peter E. Lipsky

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Objective. To delineate the phenotype and function of synovial T cells in rheumatoid arthritis (RA). Methods. T cells from normal subjects or from RA peripheral blood (PB), synovial fluid (SF), or synovial tissue (ST) were analyzed phenotypically and functionally. Results. RA SF and ST T cells were found to be markedly enriched in CD45RAdim, CD45RO+, CD45RBdim mature memory cells, whereas in the PB, CD45RAbright naive T cells were more frequent than CD45RO+ memory T cells, and only a minority were CD45RBdim. SF and ST T cells proliferated less well and produced less interleukin‐2 in response to mitogenic stimuli than did PB T cells. However, synovial T cells effectively promoted the production of Ig from normal B cells. Moreover, PB and synovial T cells differed in their capacity to down‐regulate immunoglobulin production. Anti‐CD3—stimulated PB T cells suppressed Ig production unless their proliferation was prevented with mitomycin C. In contrast, synovial T cells were potent helpers of B cell Ig production regardless of antecedent treatment with mitomycin C. To examine the relationship between the CD45RBdim phenotype and B cell help, CD45RBdim T cells were sorted from PB. As opposed to the findings with synovial T cells, suppression by control PB CD45RBdim T cells was observed, but only when large numbers were employed. B cell Ig production was enhanced after treatment of PB CD45RBdim T cells with mitomycin C. In contrast, healthy control sorted CD45RBbright or sorted CD4+, CD45RO+, CD45RBbright T cells did not support Ig secretion. After treatment with mitomycin C, both of these populations were more effective helpers of Ig production. Conclusion. RA synovium is enriched in differentiated CD45RBdim memory T cells with potent helper activity and diminished capacity to down‐regulate B cells, strongly implying an active role for these cells in the production of Ig in the synovium, and thus in the propagation of disease.

Original languageEnglish (US)
Pages (from-to)1455-1465
Number of pages11
JournalArthritis & Rheumatism
Volume35
Issue number12
DOIs
StatePublished - Dec 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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