title: MHC class II presenting cells are necessary for the induction of intrathymic tolerance.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors: J A
authors: JA
authors: Goss
authors: Y
authors: Y
authors: Nakafusa
authors: M W
authors: MW
authors: Flye
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D007519:Isoantigens / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D000961:Antilymphocyte Serum; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens