Regulatory T-cell development and function are impaired in mice lacking membrane expression of full length intercellular adhesion molecule-1

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Abstract

Summary

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-1tm1Jcgr). Compared with wild-type (ICAM-1WT) mice, ICAM-1tm1Jcgrmice 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-1tm1Jcgrmice 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 vitroactivation of CD4+ and CD8+ T cells from ICAM-1tm1Jcgrmice 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 vivoimmunization of ICAM-1tm1Jcgrmice resulted in normal generation of specific effector and memory immune responses that protect against a viral challenge. However, contrary to ICAM-1WTmice, immunization-induced specific effectors could not eradicate immunogen-expressing tumours. Treg cells from ICAM-1tm1Jcgrmice have abnormal activation and proliferation induced by anti-CD3 antibody and APCs, and have markedly decreased suppressive activityin vitro. In contrast to ICAM-1WTmice, they were unable to control experimentally induced colitisin 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.

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