caa a22 4500 475742427 CHVBK 20180406123503.0 cr unu---uuuuu 170329e20000201xx s 000 0 eng 10.1007/s002400050013 doi (NATIONALLICENCE)springer-10.1007/s002400050013 Abortive alloantigen presentation by donor dendritic cells leads to donor-specific tolerance: a study with a preoperative CTLA4Ig inoculation [Elektronische Daten] [H. Harada, H. Ishikura, I. Nakagawa, J. Shindou, M. Murakami, T. Uede, T. Koyanagi, T. Yoshiki] Donor dendritic cells (DCs) within allografts initiate the induction of an allospecific T cell response, while an abortive alloantigen presentation by DCs may induce allospecific unresponsiveness. We thus investigated the tolerogenic effect of donor DCs that were made incompetent in alloantigen presentation by treatment of CTLA4Ig. When we treated rats with donor DCs (2 × 106/rat i.v.) on the preoperative day, nine rejected allografts in an accelerated manner (5.0 ± 2.2 vs. 8.2 ± 1.6 days in the control group). Preoperative inoculation of DCs pulsed with CTLA4Ig, a procedure which suppresses an allogeneic mixed lymphocyte reaction (MLR), also provoked an accelerated rejection (5.6 ± 1.7 days). When DCs and CTLA4Ig (500 μg/rat i.p. on days −9, −7 and −5) were concomitantly inoculated, allograft survival was significantly prolonged (>38.7 ± 40.0 days); a preoperative CTLA4Ig inoculation alone failed to do so (7.5 ± 1.2 days). Long-term graft survivors tolerated skin grafts from the donor but not from those from a third party. These results indicate that abortive alloantigen presentation by donor DCs, upon which an accessory signal pathway is suppressed by CTLA4Ig, leads to prolonged graft survival and donor-specific tolerance. Springer-Verlag Berlin Heidelberg, 2000 Key words Kidney transplantation nationallicence Dendritic cell nationallicence Antigen presentation nationallicence CTLA4Ig nationallicence Donor-specific tolerance nationallicence Harada H. Departments of Urology and Pathology, Hokkaido University, Sapporo, Japan, JP aut Ishikura H. Department of Pathology, Chiba University School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan e-mail: hishik@med.m.chiba-u.ac.jp Tel.: +81-11-706-5050, Fax: +81-11-706-7825, JP aut Nakagawa I. Institute of Immunological Science, Hokkaido University, Sapporo, Japan, JP aut Shindou J. Departments of Urology and Pathology, Hokkaido University, Sapporo, Japan, JP aut Murakami M. Institute of Immunological Science, Hokkaido University, Sapporo, Japan, JP aut Uede T. Institute of Immunological Science, Hokkaido University, Sapporo, Japan, JP aut Koyanagi T. Department of Urology, Hokkaido University, Sapporo, Japan, JP aut Yoshiki T. Department of Pathology, Hokkaido University, Sapporo, Japan, JP aut https://doi.org/10.1007/s002400050013 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002400050013 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Harada H. Departments of Urology and Pathology, Hokkaido University, Sapporo, Japan, JP aut NATIONALLICENCE 700 1- Ishikura H. Department of Pathology, Chiba University School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan e-mail: hishik@med.m.chiba-u.ac.jp Tel.: +81-11-706-5050, Fax: +81-11-706-7825, JP aut NATIONALLICENCE 700 1- Nakagawa I. Institute of Immunological Science, Hokkaido University, Sapporo, Japan, JP aut NATIONALLICENCE 700 1- Shindou J. Departments of Urology and Pathology, Hokkaido University, Sapporo, Japan, JP aut NATIONALLICENCE 700 1- Murakami M. Institute of Immunological Science, Hokkaido University, Sapporo, Japan, JP aut NATIONALLICENCE 700 1- Uede T. Institute of Immunological Science, Hokkaido University, Sapporo, Japan, JP aut NATIONALLICENCE 700 1- Koyanagi T. Department of Urology, Hokkaido University, Sapporo, Japan, JP aut NATIONALLICENCE 700 1- Yoshiki T. Department of Pathology, Hokkaido University, Sapporo, Japan, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer