title: Donor T cells are not required for induction of allograft tolerance in mice treated with antilymphocyte serum, rapamycin, and donor bone marrow cells.
abstract: BACKGROUND
  Postgraft infusion of donor bone marrow cells (BMC) effectively induces tolerance to skin allografts in antilymphocyte serum- and rapamycin-treated recipients in fully major histocompatibility complex-mismatched mouse strain combinations. We used various gene knockout mice to examine the role of donor T cells and B cells in BMC-induced allograft tolerance.
  
  
  METHODS
  All recipient mice received ALS on days -1 and 2 and rapamycin (6 mg/kg) on day 7 relative to fully major histocompatibility complex-mismatched skin grafting on day 0. Donor BMC prepared either from mice lacking CD4- and/or CD8a-, or CD3epsilon-expressing cells or B cells, or from corresponding wildtype mice, were given on day 7. The level and phenotypes of chimerism was determined by flow cytometry.
  
  
  RESULTS
  All T cell- and B cell-deficient BMC were as effective as wild-type BMC in inducing prolongation of skin graft survival. A low degree of chimerism without donor type T cells was detected in tolerant mice given T cell-deficient BMC or wild-type BMC 60 days after transplantation. Chimeric cells were composed of B cells and macrophages/monocytes. Low level chimerism without donor T or B cells was also present in tolerant mice given B cell-deficient BMC.
  
  
  CONCLUSIONS
  Donor type T cells and T cell chimerism are not required for induction of allograft tolerance by the antilymphocyte serum/rapamycin/donor BMC-infusion protocol. Donor B cells also do not participate in tolerance induction. Thus, infusion of T cell-depleted BMC in conjunction with conventional immunosuppressive regimens will be a simple, safe, and effective way to induce allograft tolerance in clinical organ transplantation.
authors.affiliation: Transplant Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: A
authors.initials: A
authors.lastname: Umemura
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: T
authors.initials: T
authors.lastname: Maki
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000502:physiology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020123:Sirolimus / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000502:physiology*; D018183:Transplantation Chimera; D023001:Transplantation Tolerance / Q000187:drug effects; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D000961:Antilymphocyte Serum; D020123:Sirolimus