Influence of dendritic cells modified with costimulatory blocker cytotoxic T lymphocyte associated antigen-4 immunoglobulin on the survival of renal allografts / 中国组织工程研究

ABSTRACT

BACKGROUND: Previous studies showed that donor systemic injection of B7/CD28 costimulatory blocker cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA-4Ig) needed in T cell activation can markedly prolong the survival time of rat renal allografts, which, however, has limitations, such as high dose, extensive influence, poor specificity, systemic adverse reactions.OBJECTIVE: In order to improve the targeting of CTLA-4Ig, we modified the dendritic cells of donors and recipients in vitro with CTLA- 4Ig and observed the influence of two kinds of dendritic cells applied alone or together on the survival of renal allografis in rats.DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed between April 2003 and July 2004 at Laboratory of Department of Urinary Surgery, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.MATERIALS Kidney donor inbred Brown-Norway rats, kidney recipient inbred Lewis rats, unrelated lymphocyte donor Wistar rats.METHODS: Bone marrow derived dendritic cells of Lewis and Brown Norway rats were modified with CTLA- 4Ig gene recombinant adenovirus in vitro. Animal models of kidney transplantation were built with Brown Norway rats as donors while Lewis rats as recipients. The modified dendritic cells were injected into Lewis rats through femoral vein 24 hours before kidney transplantation alone (group 1 (n=8), donor dendritic cells; group 2 (n=8), recipient dendritic cells) and in combination (group 3 (n=8), donor and recipient dendritic cells). While the recipients without injection were used as control (group 4 (n=6)).MAIN OUTCOME MEASURES: Survival time of renal allografts; the reaction degrees of splenocytes to donor and unrelated antigen determined by MTT method on day 20 postoperation.RESULTS: Survival time of renal allografts in group 2 was not prolonged compared with group 4 while the survival time was markedly prolonged in group 3 (P < 0.01). The response of rat splenocytes to donor antigen in group 1 and group 3 was obviously lower than that in group 4 (P < 0.01), while the response to unrelated antigen was similar to group 4.CONCLUSION: Donor dendritic cells modified with CTLA- 4Ig can significantly prolonged survival time of rat renal allografts and the administration of both donor and recipient dendritic cells modified with CTLA- 4Ig can induce a longer survival time of renal allografts. Recipient dendritic cells cannot prolong the survival time of renal allografts.