Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis

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+, CD45RB-mature memory cells, whereas in the PB, CD45RAbdght naive T cells were more frequent than CD45RO+ memory T cells, and only a minority were CD45RBm. 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 CD45RBdh phenotype and B cell help, CD45RBdi" T cells were sorted from PB. As opposed to

Section: Resultssupporting

confidence: 88%

“…For this purpose, the analysis of the expression of the isoforms of CD45 is of particular value. Synovial T cells are known to be enriched in CD45RO+ memory T cells compared with PB T cells (19,20). Memory T cells in humans can now be defined more completely by MAb that recognize the products of the B exon of the CD45 gene.…”

mentioning

confidence: 99%

Rheumatoid synovium is enriched in CD45RB^dim mature memory T cells that are potent helpers for B cell differentiation

Thomas

McIlraith

Davis

et al. 1992

“…among RA patients (P < 0.01), confirming the observations of others (10). Similar alterations in CD7 expression were seen when CD4+ cells were divided into CD29high and CD29"" subgroups in the 3-color FACS analyses (results not shown).…”

Section: Cd7-t Cells and Induction Of Pokeweed Mitogen-supporting

confidence: 90%

CD7– T cells in rheumatoid arthritis

Lazarovits¹,

White²,

Karsh³

1992

Objective. Rheumatoid arthritis (RA) is characterized by decreased expression of CD7 in the peripheral blood and in the synovium. The present study was designed to identify the basis for and functional consequences of this decreased expression.Methods. Peripheral blood lymphocytes from normal controls and from patients with RA or systemic lupus erythematosus (SLE), and T cell lines derived from rheumatoid synovium, were evaluated using 3‐color fluorescence‐activated cell sorter analysis.Results. Normal subjects and most SLE patients expressed homogeneous, bright CD7 on CD4+, CD45RA+ cells, whereas RA patients demonstrated a significantly increased proportion of CD7– cells. T cell lines derived from rheumatoid synovium demonstrated a striking deficiency of CD7 on CD4+, CD45RA– cells. CD4+, CD45RA+ cells from RA patients changed phenotype after in vitro activation to CD45RA negativity, with up‐regulation of CD7. CD7–, CD4+, CD45RA– cells were assessed for their ability to induce pokeweed mitogen‐driven IgM and IgM‐rheumatoid factor synthesis, and they were found to be potent helper/inducer cells. An increased population of CD7‐, CD4+ cells in peripheral blood was found to predict a low response to recall antigens.Conclusion. The low expression of CD7 in RA may explain some of the immune abnormalities which may contribute to the pathogenesis of this disease.

“…The naive subset has been shown to be greatly reduced in RA synovial fluid (18,19) and in peripheral blood (18). Thus far, despite intensive but conflicting investigations, no definite functional subpopulation has been distinguished.…”

Section: T Cell Receptor Expression and Activation Of Synovial Lymphomentioning

confidence: 99%

T Cell Receptor Expression And Activation Of Synovial Lymphocyte Subsets In Patients With Rheumatoid Arthritis

Rème

Portier

Frayssinoux

et al. 1990

Two-color flow cytometry analysis of peripheral blood and synovial lymphocytes from rheumatoid arthritis patients was performed using monoclonal antibodies directed against T cell subsets, T cell activation markers, and T cell receptors. The results showed an abnormally high percentage (>15%) of CD3+, CD4-, and CDS-T cells expressing a specific receptor containing a y chain. Phenotypic analysis of lymphocytes infiltrating both knee joints of individual rheumatoid arthritis patients revealed very similar subset distribution and activation levels, despite strong differences in the clinical status between the 2 sites.