The Role of CD26/DPP IV in Preservation of Early Pulmonary Graft Function

CD26 plays a pivotal role in thymic differentation/maturation (Simeoni et al 2002), costimulation (Morimoto 1998), migration (Ikushima et al 2003) and the T cell memory response (De Meester et al 1999). In addition, it possesses enzymatic activity (dipeptidyl peptidase IV, DPP IV), which is linked to its costimulatory efficacy (Tanaka et al 1993, 1994), and has been correlated with immunological competence in vivo (Vanham et al 1993). Circulating DPP IV enzymatic activity is increased in various immune disorders (Fujita et al 1978; Constantinescu et al 1995). We have previously shown that the course of acute cardiac allograft rejection in rats is associated with a significant increase in DPP IV serum activity. Specifically inhibiting DPP IV circulating activity in transplant recipients impaired cellular and humoral immune responses, significantly prolonging graft survival in models of acute cardiac rejection (Korom et al 1997). Following successful kidney transplantation (Tx) in patients on maintenance immunosuppression, systemic DPP IV catalytic activity was markedly reduced for twelve months, and CD26 surface expression on circulating lymphocytes displayed a significant down-regulation for eighteen months post Tx (Korom et al 2002). To further analyze the influence of DPP IV targeted inhibition on the course of early allograft performance, we chose lung Tx in the rat as an alternative model of perfused organ engraftment. In contrast to the heart, the lung constitutes a more challenging immunological set up, due to its vast area of interaction with the milieu exterieur. In this study we demonstrate that specifically targeting circulating DPP IV enzymatic activity in LEW recipients of LBNF1 pulmonary grafts maintains pulmonary macromorphological architecture and preserves ventilatory parameters for up to five days following Tx.