Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.

Laffón, A; García‐Vicuña, Rosario; Humbría, Alicia; Postigo, Antonio; Corbí, Ángel L.; Landázuri, Manuel O.; Sánchez-Madrid, Francisco

doi:10.1172/jci115338

Cited by 197 publications

(117 citation statements)

References 50 publications

(38 reference statements)

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“…Of relevance is the reported observation that in serial synovial biopsies from patients who responded to gold salt therapy with a clinical reduction in joint inflammation, there was reduced expression of ELAM-1, but no change in the mononuclear cell infiltrate in the membrane (31). We (19) and others (32) have also shown that lymphocytes and macrophages in rheumatoid synovial tissues appear to express high levels of the PI-integrin VLA-4, the known leukocyte receptor for VCAM-1. A study measuring the adherence of lymphocytes to frozen sections of rheumatoid synovial tissue has indicated that VLA-WVCAM-1 interactions appear to be of primary importance in lymphocyte homing to rheumatoid synovium (33).…”

Section: Discussionsupporting

confidence: 54%

Expression of ICAM‐R (ICAM‐3), a novel counter‐receptor for LFA‐1, in rheumatoid and nonrheumatoid synovium

El‐Gabalawy¹,

Gallatin²,

Vazeux³

et al. 1994

Arthritis & Rheumatism

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Objective. To study the distribution of intercellular adhesion molecule receptor (ICAM-R, or ICAM3), a novel ligand for the leukointegrin lymphocyte function-associated antigen 1 (LFA-l), in normal and rheumatoid synovial membranes and to compare this with the distribution of ICAM-1, ICAM-2, vascular cell adhesion molecule 1 (VCAM-l), and endothelial leukocyte adhesion molecule 1 (ELAM-1).Methods. We performed immunohistochemical analyses of frozen sections of normal and rheumatoid synovial tissue using monoclonal antibodies to the molecules examined.Results. ICAM-1 staining was detectable on the vascular endothelium and the synovial lining cells of both normal and rheumatoid synovial membranes. A variable proportion of lymphocytes infiltrating rheumatoid tissues expressed ICAM-1. ICAM-2 staining was demonstrable in the vascular endothelium of both normal and inflamed tissues, the latter demonstrating a significantly higher proportion of positive vessels. ELAM-1 staining was not detectable in normal synovial membranes but was seen on the endothelium of a limited number of rheumatoid synovial vessels, usually close to the synovial lining cell layer. VCAM-1 staining was intense in both normal and rheumatoid synovial lining cells, but vascular staining was weak in both. In conHani El-Gabalawy, MD: The University of Manitoba, Winnipeg, Manitoba, Canada; Michael Gallatin, PhD: ICOS Corporation, Seattle, Washington; Rosemay Vazeux, PhD: ICOS Corporation; Gary Peterman, PhD: ICOS Corporation; John Wilkins, P h D University of Manitoba.Address reprint requests to Hani El-Gabalawy, MD, Rheumatic Disease Unit, 800 Sherbrook Street, Winnipeg, Manitoba R3A 1M4, Canada.Submitted for publication March 31, 1993; accepted in revised form November 30, 1993. trast, ICAM-R staining was not detected in association with any synovial blood vessels, but was widely expressed by lymphocytes and macrophages. Cells of the lining layer did not stain for ICAM-R.Conclusion. Although ICAM-R is a ligand for LFA-1 and shares considerable sequence homology with ICAM-1 and ICAM-2, it does not appear to be expressed by the endothelium of normal or inflamed synovial vessels. Intense expression of ICAM-R by rheumatoid synovial lymphocytes and macrophages suggests that it may play a role in processes requiring cell-cell contact, such as antigen presentation and homotypic aggregation.Chronic inflammatory lesions such as rheumatoid synovitis require ongoing recruitment and retention of leukocytes from the vascular space. A critical initial step involves the adhesion of leukocytes to vascular endothelium (1-3). This is currently thought to be regulated by a cascade of molecular interactions occurring between leukocyte membrane receptors and endothelial counter-receptors, many of which are inducible in their expression. Several endothelial adhesion molecules have been well characterized and shown to participate in leukocyte attachment. These include the endothelial leukocyte adhesion molecule 1 (ELAM-1, or E-selectin) (4), intercellular adhesion molec...

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Section: Discussionsupporting

confidence: 54%

Expression of ICAM‐R (ICAM‐3), a novel counter‐receptor for LFA‐1, in rheumatoid and nonrheumatoid synovium

El‐Gabalawy¹,

Gallatin²,

Vazeux³

et al. 1994

Arthritis & Rheumatism

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“…n Ն 6 mice for each genotype. arthritis patients (69), and strikingly, these included an unusual CD69 ϩ /CD25 Ϫ T cell subset (70). CD4 T cell activation was apparent in the youngest animals examined (6 wk) and did not show a significant increase as the mice aged up to 12 wk.…”

Section: T Cell Activation In Lpr/lpr Micementioning

confidence: 92%

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

Fields

Sokol

Eaton-Bassiri

et al. 2001

The Journal of Immunology

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Autoantibodies directed against dsDNA are found in patients with systemic lupus erythematosus as well as in mice functionally deficient in either Fas or Fas ligand (FasL) (lpr/lpr or gld/gld mice). Previously, an IgH chain transgene has been used to track anti-dsDNA B cells in both nonautoimmune BALB/c mice, in which autoreactive B cells are held in check, and MRL-lpr/lpr mice, in which autoantibodies are produced. In this study, we have isolated the Fas/FasL mutations away from the autoimmune-prone MRL background, and we show that anti-dsDNA B cells in Fas/FasL-deficient BALB/c mice are no longer follicularly excluded, and they produce autoantibodies. Strikingly, this is accompanied by alterations in the frequency and localization of dendritic cells as well as a global increase in CD4 T cell activation. Notably, as opposed to MRL-lpr/lpr mice, BALB-lpr/lpr mice show no appreciable kidney pathology. Thus, while some aspects of autoimmune pathology (e.g., nephritis) rely on the interaction of the MRL background with the lpr mutation, mutations in Fas/FasL alone are sufficient to alter the fate of anti-dsDNA B cells, dendritic cells, and T cells.

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“…T lymphocytes derived from RA synovial tissue display markers of recent activation, including up-regulation of HLA class II proteins and very late activation antigen 4 integrins (4,5). Consistent with this activated phenotype, RA synovial T lymphocytes can stimulate monocyte tumor necrosis factor ␣ (TNF␣) production in a cell-cell-dependent manner (6).…”

Section: Synovial Adherent Cells and This Correlated With T Cell Mitmentioning

confidence: 97%

CTLA‐4IG suppresses reactive oxygen species by preventing synovial adherent cell–induced inactivation of rap1, a ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells

Remans¹,

Wijbrandts²,

Sanders³

et al. 2006

Arthritis & Rheumatism

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Objective. Oxidative stress contributes to the inflammatory properties of rheumatoid arthritis (RA) synovial T lymphocytes. This study was undertaken to investigate the mechanisms leading to production of reactive oxygen species (ROS) and oxidative stress in RA synovial T lymphocytes.Methods. ROS production in T lymphocytes from the peripheral blood (PB) of healthy donors and from the PB and synovial fluid (SF) of RA patients was measured by ROS-dependent fluorescence of 6-carboxy-2 ,7 -dichlorofluorescein. Rap1 GTPase activation was assessed by activation-specific probe precipitation. Proliferation of RA PB and SF T lymphocytes was assayed by 3 H-thymidine incorporation. In some experiments, RA PB T cells were preincubated with autologous SF or with PB or SF adherent cells. Experiments were performed in the absence or presence of transwell membranes or CTLA-4Ig fusion proteins. Short-and longterm stimulations of healthy donor PB T lymphocytes were performed with inflammatory cytokines, in the absence or presence of activating anti-CD28 antibodies. Conclusion. Cell-cell contact between T cells and RA synovial adherent cells mediates Rap1 inactivation and subsequent ROS production in T lymphocytes following exposure to inflammatory cytokines. This process can be blocked by CTLA4-Ig fusion protein. Results. T lymphocyte ROS production and

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Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.

Cited by 197 publications

References 50 publications

Expression of ICAM‐R (ICAM‐3), a novel counter‐receptor for LFA‐1, in rheumatoid and nonrheumatoid synovium

Expression of ICAM‐R (ICAM‐3), a novel counter‐receptor for LFA‐1, in rheumatoid and nonrheumatoid synovium

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

CTLA‐4IG suppresses reactive oxygen species by preventing synovial adherent cell–induced inactivation of rap1, a ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells

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