TY - JOUR T1 - Regulatory T-cell development and function are impaired in mice lacking membrane expression of full length intercellular adhesion molecule-1. JF - Immunology Y1 - 2015 A1 - Gottrand, Gaelle A1 - Courau, Tristan A1 - Thomas-Vaslin, Véronique A1 - Prevel, Nicolas A1 - Vazquez, Thomas A1 - Ruocco, Maria Grazia A1 - Bénédicte Lambrecht A1 - Bellier, Bertrand A1 - Colombo, Bruno M A1 - Klatzmann, David KW - Animals KW - Calcium KW - Cell Differentiation KW - Cell Membrane KW - Colitis KW - Disease Models, Animal KW - Female KW - Gene Expression KW - Intercellular Adhesion Molecule-1 KW - Lymphocyte Activation KW - mice KW - Mice, Transgenic KW - T-Lymphocyte Subsets KW - T-Lymphocytes, Regulatory KW - Thymocytes AB -

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.

VL - 146 CP - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26370005?dopt=Abstract M3 - 10.1111/imm.12533 ER -