Suppressed alloreactivity and mixed chimerism in rats with accepted cardiac allografts by intrathymic injection of donor bone marrow cells

Abstract Intrathymic injection of donor bone marrow cells (ITBMCs) at the time of transplantation and treatment with antilymphocyte serum (ALS) permitted the indefinite survival of Brown Norway (BN, RT1n) rat heart grafts in 6 out of 8 Lewis (LEW, RT1l) rat recipients. LEW recipients with long-surviving BN heart grafts (LSGs) also accepted additional BN heart grafts without further immunosuppression, though they rejected Piebald Virol Glaxo (PVG, RT1c) rat heart grafts in the usual fashion. In the in vitro study, the proliferative response of the lymphocytes from LEW recipients with LSGs remained suppressed when they were stimulated by BN spleen cells, but not when stimulated by PVG cells. Bone marrow cells (BMCs) from LEW rats with LSGs showed strong, nonspecific, suppressive effects on the proliferative response in the mixed lymphocyte culture reaction, suggesting that one of the possible explanations for tolerance might be the involvement of a suppressor mechanism.

[1]  I. Heron.  A technique for accessory cervical heart transplantation in rabbits and rats. , 2009, Acta pathologica et microbiologica Scandinavica. Section A, Pathology.

[2]  J. Kupiec-Weglinski,et al.  The alloantibody network following intrathymic immunomodulation of sensitized rat recipients of cardiac allografts. , 1995, Transplantation.

[3]  M. W. Flye,et al.  Generation of suppressor cells maintains donor-specific tolerance after intrathymic injection of alloantigen. , 1995, Transplantation proceedings.

[4]  S. Oluwole,et al.  Effectiveness of intrathymic inoculation of soluble antigens in the induction of specific unresponsiveness to rat islet allografts without transient recipient immunosuppression. , 1994, Transplantation.

[5]  T. Akiyama,et al.  Heterotopic rat heart transplantation to the iliac vessels. , 1994, Transplantation proceedings.

[6]  T. Kurita,et al.  Mixed chimerism demonstrated in rats which have accepted heart allografts by intrathymic administration of bone marrow cells. , 1994, Transplantation proceedings.

[7]  H. Kanda,et al.  Organ-specific tolerance induced by intrathymic injection of donor bone marrow cells and FK 506 or antilymphocyte serum in rat heart transplantation. , 1994, Transplantation proceedings.

[8]  S. Knechtle,et al.  Induction of specific tolerance by intrathymic injection of recipient muscle cells transfected with donor class I major histocompatibility complex. , 1994, Transplantation.

[9]  T. Kurita,et al.  Organ-specific unresponsiveness induced by intrathymic injection of donor bone marrow cells and a short course of immunosuppression in the rat heart transplantation model. , 1993, Transplant immunology.

[10]  H. Kanda,et al.  Prolonged survival of rat cardiac allografts induced by intrathymic injection of donor bone marrow cells. , 1993, Transplantation proceedings.

[11]  A. Posselt,et al.  Examination of the Mechanisms Responsible for Tolerance Induction After Intrathymic Inoculation of Allogeneic Bone Marrow , 1993, Annals of surgery.

[12]  R. Fawwaz,et al.  INDUCTION OF DONOR‐SPECIFIC UNRESPONSIVENESS TO RAT CARDIAC ALLOGRAFTS BY INTRATHYMIC INJECTION OF UV‐B‐IRRADIATED DONOR SPLEEN CELLS , 1993, Transplantation.

[13]  J. Markmann,et al.  Promotion of rat cardiac allograft survival by intrathymic inoculation of donor splenocytes. , 1993, Transplantation.

[14]  T. Mohanakumar,et al.  Induction of donor-specific tolerance to cardiac but not skin or renal allografts by intrathymic injection of splenocyte alloantigen. , 1993, Transplantation.

[15]  J. Markmann,et al.  Deletion of donor-reactive T lymphocytes in adult mice after intrathymic inoculation with lymphoid cells. , 1993, Transplantation.

[16]  F. Ramsdell,et al.  Maintenance of in Vivo Tolerance by Persistence of Antigen , 1992, Science.

[17]  A. Posselt,et al.  Induction of donor-specific tolerance to rat cardiac allografts by intrathymic inoculation of bone marrow. , 1992, Surgery.

[18]  T. Starzl,et al.  Cell migration, chimerism, and graft acceptance , 1992, The Lancet.

[19]  A. Monaco.  Studies in rodents on the use of polyclonal antilymphocyte serum and donor-specific bone marrow to induce specific unresponsiveness to skin allografts. , 1991, Transplantation proceedings.

[20]  M. Choti,et al.  Induction of donor-specific unresponsiveness by intrathymic islet transplantation. , 1990, Science.

[21]  G. Mayrhofer,et al.  Bone marrow origin of Ia-positive cells in the medulla rat thymus , 1981, The Journal of experimental medicine.

[22]  A. Fabrega,et al.  Intrathymic injection of alloantigen. , 1995, Transplantation.