Lack of cognate help by CD4+ T cells and anergy of CD8+ T cells are the principal mechanisms for anti-leukocyte function-associated antigen-1/intercellular adhesion molecule-1-induced cardiac allograft tolerance

Transplantation
H BashudaK Okumura

Abstract

Combined treatment with anti-leukocyte function-associated antigen-1 (LFA-1) and anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies leads to allograft tolerance in murine cardiac transplantation. In the present study, we analyzed the mechanisms for this tolerance induction. In the tolerant mice, proliferative response of splenic T cells against donor-type cardiac myocytes and of CD8+ T cells against donor-type alloantigens was impaired as compared with responses in naive or rejected mice, but was completely restored with exogenous interleukin 2. This suggests that class I-restricted CD8+ T cells of tolerant mice were rendered anergic against donor-type alloantigens in the periphery. In contrast, proliferative response of CD4+ T cells against donor-type alloantigens in vitro was comparable between tolerant and naive mice. When heart and skin grafts from the same donor (BALB/c [H2d]) were simultaneously transplanted to C3H mice (H2k), both were rejected within 29 days, even though the mice were similarly treated with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies. In contrast, when heart graft from BALB/c and skin graft from third-party donor (C57BL/6 [H2b]) were simultaneously transplanted to C3H mice under ...Continue Reading

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Citations

Dec 20, 2000·Transplantation Proceedings·M KatoS Ohshima
Dec 26, 2001·Transplantation Proceedings·S OhshimaN Nishiyama
Dec 5, 1998·Transplantation Proceedings·H DegawaT Nagao
Oct 9, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Willy AasebøKnut Stavem
Jan 11, 2000·Transplantation·Q GaoE H Field
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·K I SeinoK Okumura
Oct 6, 1998·Cellular Immunology·E PeterssonH Ekberg
Mar 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M R NicollsR G Gill
Oct 12, 2021·Frontiers in Immunology·Chitavi D MaullooJeffrey A Hubbell

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