title: Regulatory T-cell development and function are impaired in mice lacking membrane expression of full length intercellular adhesion molecule-1.
abstract: To further investigate the contribution of intercellular adhesion molecule-1 (ICAM-1) to adaptive immune responses, we analysed T-cell development and function in mice lacking full-length ICAM-1 (ICAM-1(tm1Jcgr) ). Compared with wild-type (ICAM-1(WT) ) mice, ICAM-1(tm1Jcgr) mice have impaired thymocyte development. Proportions and numbers of double negative, double positive, mature CD4(+) and CD8(+) thymocytes, as well as of regulatory T (Treg) cells were also significantly decreased. In the periphery, ICAM-1(tm1Jcgr) mice had significantly decreased proportions and numbers of naive and activated/memory CD4(+) and CD8(+) T cells, as well as of Treg cells, in lymph nodes but not in the spleen. In vitro activation of CD4(+) and CD8(+) T cells from ICAM-1(tm1Jcgr) mice with anti-CD3 antibodies and antigen-presenting cells (APCs) resulted in a significantly weaker proliferation, whereas proliferation induced with anti-CD3 and anti-CD28 antibody-coated beads was normal. In vivo immunization of ICAM-1(tm1Jcgr) mice resulted in normal generation of specific effector and memory immune responses that protect against a viral challenge. However, contrary to ICAM-1(WT) mice, immunization-induced specific effectors could not eradicate immunogen-expressing tumours. Treg cells from ICAM-1(tm1Jcgr) mice have abnormal activation and proliferation induced by anti-CD3 antibody and APCs, and have markedly decreased suppressive activity in vitro. In contrast to ICAM-1(WT) mice, they were unable to control experimentally induced colitis in vivo. Hence, our results further highlight the pleiotropic role of ICAM-1 in T-cell-dependent immune responses, with a major role in Treg cell development and suppressive function.
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Gottrand
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Courau
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Thomas-Vaslin
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Prevel
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vazquez
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ruocco
authors.affiliation: CODA-CERVA-VAR, Brussels, Belgium.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Lambrecht
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bellier
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Colombo
authors.affiliation: Immunology-Immunopathology-Immunotherapy, UPMC Univ Paris 06, UMRS_959, Sorbonne Universités, Paris, France.|Immunology-Immunopathology-Immunotherapy, FRE3632, CNRS, Paris, France.|Immunology-Immunopathology-Immunotherapy, UMRS_959, INSERM, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism*; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D018799:Intercellular Adhesion Molecule-1; D002118:Calcium
keywords: adhesion molecules; autoimmunity; cell activation; cell differentiation; tolerance