Intratracheal delivery of a single major histocompatibility complex class I peptide induced prolonged survival of fully allogeneic cardiac grafts and generated regulatory cells

We have previously reported that intratracheal delivery of donor splenocytes in mice induces hyporesponsiveness to fully allogeneic cardiac grafts and generates regulatory cells. Here, we examined whether an allopeptide would produce the same results. A 15-mer (54–68) peptide corresponding to a hypervariable region of the Kb molecule was given intratracheally or intravenously to CBA (H2k) mice 7 days before transplantation of a C57BL/10 (H2b) or BALB/c (H2d) heart and was also used in adoptive transfer experiments. Cardiac grafts in recipients given Kb peptide intratracheally experienced a median survival time (MST) of 56 days, whereas those in recipients given the peptide intravenously were rejected acutely (MST=7.5 days). Adoptive transfer of splenocytes from mice pretreated intratracheally with Kb peptide to nai¨ve secondary recipients prolonged survival of cardiac grafts (MST = 35 days). Intratracheal delivery of a single major histocompatibility complex class I peptide induced hyporesponsiveness to allogeneic cardiac grafts and generated regulatory cells. [Copyright &y& Elsevier]