MHC class II presenting cells are necessary for the induction of intrathymic tolerance

Ann Surg. 1993 May;217(5):492-9; discussion 499-501. doi: 10.1097/00000658-199305010-00009.

Abstract

Objective: This study determined the form of cellular donor MHC alloantigen necessary for the induction of intrathymic tolerance.

Background: The authors have achieved indefinite donor-specific tolerance, to a fully MHC-disparate rat heterotopic cardiac allograft, after the pretransplant intrathymic injection of unfractionated donor splenocytes and a single injection of rabbit anti-rat lymphocyte serum (ALS), without subsequent immunosuppression.

Methods: Male 4-12-week-old Buffalo (RT1b) rats underwent an intrathymic injection of either fractionated Lewis (RT1(1)) red blood cells (purified by Ficoll gradient) or T lymphocytes (purified by nylon wool column and plastic adherence), both of which express only MHC class I alloantigens, or B lymphocytes, macrophages, and dendritic cells (purified by plastic adherence) which express both MHC class I and class II alloantigens. At the completion of alloantigen injection the Buffalo recipient rats were given 1 ml of ALS intraperitoneally. Twenty-one days later a heterotopic Lewis heart was transplanted.

Results: The intrathymic injection of the fractions of Lewis MHC class I and class II expressing B lymphocytes, macrophages, and dendritic cells induced a donor-specific tolerance that resulted in indefinite Lewis cardiac allograft survival (MST > 125 days) in all recipients without further immunosuppression, whereas groups receiving MHC class I expressing red blood cell or T lymphocyte injections plus ALS rejected Lewis cardiac allografts with a MST of 7.3 and 16.5 days, respectively, thus indicating that the MHC class II expressing cell is necessary for the induction of intrathymic tolerance. Buffalo recipients with a long-term surviving Lewis cardiac allograft, after Lewis MHC class II expressing cells were still able to reject a third-party heterotopic ACI (RT1a) cardiac allograft in normal time (MST = 7.0 days), but did not reject a second Lewis cardiac allograft (MST > 100 days). Additionally, the intrathymic injection of MHC class II expressing cells resulted in decreased interleukin-2 (IL-2) production and an 80% decrease in in vitro donor-specific cell mediated cytotoxicity, whereas the cytolytic response to a third party was unaltered.

Conclusion: Donor MHC class II, and not class I, expressing cells are the cells in donor splenocytes, injected intrathymically, responsible for the development of donor-specific allograft tolerance.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antilymphocyte Serum / administration & dosage
  • Graft Survival / immunology*
  • Heart Transplantation / immunology*
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II / immunology*
  • Immune Tolerance
  • Isoantigens / administration & dosage
  • Isoantigens / immunology*
  • Male
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred BUF
  • Rats, Inbred Lew
  • Spleen / cytology
  • Spleen / immunology
  • Thymus Gland / immunology*
  • Tissue Donors
  • Transplantation, Homologous / immunology

Substances

  • Antilymphocyte Serum
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Isoantigens