Contributions of direct and indirect alloresponses to chronic rejection of kidney allografts in nonhuman primates |
| |
Authors: | Nadazdin Ognjenka Boskovic Svjetlan Wee Siew-Lin Sogawa Hiroshi Koyama Ichiro Colvin Robert B Smith R Neal Tocco Georges O'Connor David H Karl Julie A Madsen Joren C Sachs David H Kawai Tatsuo Cosimi A Benedict Benichou Gilles |
| |
Institution: | Department of Surgery, Transplant Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. |
| |
Abstract: | The relative contribution of direct and indirect allorecognition pathways to chronic rejection of allogeneic organ transplants in primates remains unclear. In this study, we evaluated T and B cell alloresponses in cynomolgus monkeys that had received combined kidney/bone marrow allografts and myeloablative immunosuppressive treatments. We measured donor-specific direct and indirect T cell responses and alloantibody production in monkeys (n = 5) that did not reject their transplant acutely but developed chronic humoral rejection (CHR) and in tolerant recipients (n = 4) that never displayed signs of CHR. All CHR recipients exhibited high levels of anti-donor Abs and mounted potent direct T cell alloresponses in vitro. Such direct alloreactivity could be detected for more than 1 y after transplantation. In contrast, only two of five monkeys with CHR had a detectable indirect alloresponse. No indirect alloresponse by T cells and no alloantibody responses were found in any of the tolerant monkeys. Only one of four tolerant monkeys displayed a direct T cell alloresponse. These observations indicate that direct T cell alloresponses can be sustained for prolonged periods posttransplantation and result in alloantibody production and chronic rejection of kidney transplants, even in the absence of detectable indirect alloreactivity. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|