title: A hierarchy for integrin expression and adhesiveness among T cell subsets that is linked to TCR gene usage and emphasizes V delta 1+ gamma delta T cell adherence and tissue retention.
abstract: To define the relationship between T cell phenotype and adhesiveness, we examined T cell adhesion to endothelial cell, fibroblast, and epithelial cell monolayers as well as extracellular matrix proteins (collagen and fibronectin) using a three-color flow cytometry-based adherence assay that minimizes basal adhesion levels and facilitates quantitative lymphocyte subtyping. Regardless of monolayer type, monolayer stimulation conditions, or T cell activation status, we found that the gamma delta-TCR-bearing T cells adhered more efficiently than alpha beta T cells. The difference was based predominantly on increased levels of activatable LFA-1 (and to a lesser degree VLA-4) because: 1) it correlated precisely with inhibitability by anti-LFA-1 (and VLA-4) mAbs and the levels of LFA-1 (and VLA-4) on the cell surface, and 2) it persisted after maximal LFA-1 (and VLA-4) activation with phorbol dibutyrate. In contrast to most cases of alpha beta T cell behavior, gamma delta T cell adhesion to cell monolayers was not linked to memory status, i.e., there was no difference between naive V delta 1+ and memory V delta 2+ populations in levels of LFA-1 (or VLA-4) expression or LFA-1- (or VLA-4-) dependent adhesion to cell monolayers. However, V delta 1+ cells exhibited higher levels of VLA-5 that correlated with an increased adhesiveness to fibronectin and to a 120-kDa fibronectin fragment (FN-120) that contains only the VLA-5-binding domain but not to type I collagen or to a fibronectin fragment (FN-40) that binds only VLA-4. Taken together, the results define a hierarchy for integrin (LFA-1, VLA-4, and VLA-5) expression and consequent adhesion among T cell subsets that is linked to TCR gene usage (but not necessarily linked to memory status) and may thereby help to explain the accumulation and retention of V delta 1+ gamma delta T cells in epithelial and connective tissues.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nakajima
authors.forename: W T
authors.initials: WT
authors.lastname: Roswit
authors.forename: D C
authors.initials: DC
authors.lastname: Look
authors.forename: M J
authors.initials: MJ
authors.lastname: Holtzman
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D015329:Gene Rearrangement, T-Lymphocyte; D007156:Immunologic Memory; D016023:Integrins / Q000096:biosynthesis* / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis* / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000502:physiology; D017469:Receptors, Fibronectin / Q000096:biosynthesis* / Q000235:genetics; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017469:Receptors, Fibronectin; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D003094:Collagen