Role of Integrin αE(CD103)β7 for Tissue-Specific Epidermal Localization of CD8+ T Lymphocytes
- 1 September 2001
- journal article
- Published by Elsevier BV in Journal of Investigative Dermatology
- Vol. 117 (3), 569-575
- https://doi.org/10.1046/j.0022-202x.2001.01481.x
Abstract
Tissue-specific T cell localization is crucial for immune surveillance of normal tissues and the pathogenesis of inflammatory disorders. In psoriatic skin, CD8+ lymphocytes predominantly reside within the epidermis, whereas CD4+ T cells are most abundant within the dermis. Molecular mechanisms guiding this spatial compartmentalization are not completely understood, however. Here, we demonstrate that 55% (±9.7%, n = 14) of the epidermal T cells, predominantly of the CD8+ phenotype, expressed the integrin αE(CD103)β7. In contrast, only 5% (±2.0%) of the dermal T cells were αE(CD103)β7+. Integrin αE(CD103)β7 was not detected in normal skin (n = 10), and less than 1% of peripheral blood lymphocytes derived from normal (n = 11) or psoriatic (n = 10) donors expressed αE(CD103). When cultured T lymphoblasts (n = 12 donors) were stimulated with transforming growth factor β1, expression of integrin αE(CD103)β7 was induced on 52.8% (±16.2%) of CD8+ cells, but only on 6.1% (±2.3%) of CD4+ cells, suggesting selective inducibility on CD8+ lymphocytes. Whereas similar overall expression of transforming-growth-factor-β1-specific mRNA was detected in normal and psoriatic skin by real-time quantitative polymerase chain reaction, immunohistochemistry revealed focal overexpression of transforming growth factor β1 underneath psoriatic, but not normal, epidermis. This heterogenous transforming growth factor β1 expression may contribute to induction of αE(CD103) in vivo. Adhesion of transforming-growth-factor-β1-stimulated CD8+, but not CD4+, T cells to cultured keratinocytes and psoriatic epidermis in frozen sections could be significantly inhibited by antibodies that blocked the αE(CD103)/E–cadherin interaction. Co-culture of lymphoblasts and keratinocytes resulted in marginal enhancement of αE(CD103)β7 expression in some cases. Overall, integrin αE(CD103)β7 appears to contribute to tissue-specific epidermal localization of CD8+ T lymphocytesKeywords
This publication has 52 references indexed in Scilit:
- Alpha E beta 7Molecular Pathology, 1999
- Identification of a Binding Site for Integrin αEβ7 in the N-terminal Domain of E-cadherinPublished by Elsevier BV ,1996
- The role of alphaEbeta7 integrin (CD103) and E-cadherin in epidermotropism in cutaneous T-cell lymphomaJournal of Cutaneous Pathology, 1996
- Expression of the Human Mucosal Lymphocyte Antigen, HML‐1, by T Cells Activated with Mitogen or Specific Antigen In VitroScandinavian Journal of Immunology, 1995
- Investigation of epidermotropism in canine mycosis fungoides: Expression of intercellular adhesion molecule-1 (ICAM-1) and beta-2 integrinsArchiv für dermatologische Forschung, 1995
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994
- Integrins: Versatility, modulation, and signaling in cell adhesionCell, 1992
- VLA Proteins in the Integrin Family: Structures, Functions, and Their Role on LeukocytesAnnual Review of Immunology, 1990
- Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal inflamed skin: Modulation by recombinant gamma interferon and tumor necrosis factorJournal of the American Academy of Dermatology, 1989
- Adhesion molecule mapping in normal human skinArchiv für dermatologische Forschung, 1989