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

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.

%B Immunology %V 146 %P 657-70 %8 2015 Dec %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26370005?dopt=Abstract %R 10.1111/imm.12533