The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium

Authors

  • John J. Cush MD,

    1. Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, Texas
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  • Peter Pietschmann MD,

    Corresponding author
    1. Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, Texas
    • Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235
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  • Nancy Oppenheimer-Marks PhD,

    1. Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, Texas
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  • Peter E. Lipsky MD

    1. Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas, Texas
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Abstract

Objective. Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites.

Methods. The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed.

Results. Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29bright, CD11abright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA—DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2–3-fold increase in migratory capacity over normal and RA PBTL.

Conclusion. These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin—. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.

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