Dual function of the extracellular matrix: stimulatory for cell cycle progression of naive T cells and antiapoptotic for tissue-derived memory T cells.
Tissue T cells encounter Ag in a distinct microenvironment, where they are embedded in the interstitial extracellular matrix (ECM). In contrast, while naive T cells are exposed to Ag in the lymph node, immediately after naive T cells are activated they must extravasate into the ECM to function effectively. Because integrin-mediated adhesion to the ECM modulates cell cycle progression and survival in adherent nonimmune cells, we hypothesize that blood and tissue-derived T cells have similarly adapted their behavior to their first or continued encounter with ECM. T cells from peripheral blood (PBT) and tissue (the intestinal lamina propria T cell (LPT)) were stimulated with anti-CD3-coated beads in the presence or absence of native ECM derived from intestinal fibroblasts, plate-immobilized fibronectin, or collagen type I. Native ECM and collagen, but not fibronectin, induced in anti-CD3 activated PBT a 4- to 5-fold increase in the entry, progression, and completion of the cell cycle over that triggered by anti-CD3 alone. Neutralizing beta1 integrin Abs abrogated this increase. None of these ECM proteins stimulated cell cycle progression in LPT. In contrast, anti-CD3 activation of LPT in the presence of native ECM and fibronectin reduced activation-induced cell death by 40%. These results demonstrate that naive and effector/memory T cells respond differently upon exposure to specific ECM components. When naive PBT encounter Ag in the context of ECM, their progression through the cell cycle is enhanced, favoring clonal expansion; while tissue T cell longevity may be mediated by interactions with the ECM.
Sturm
Andreas
A
Department of Medicine, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, OH 44106, USA.
Krivacic
Kimberley A
KA
Fiocchi
Claudio
C
Levine
Alan D
AD
D000276:Adjuvants, Immunologic / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002449:Cell Aggregation / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D019012:Integrin beta1 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007399:Interphase / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009928:Organ Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology*
D000276:Adjuvants, Immunologic; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D006131:Growth Inhibitors; D019012:Integrin beta1