Donor T cells are not required for induction of allograft tolerance in mice treated with antilymphocyte serum, rapamycin, and donor bone marrow cells.
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.
Umemura
A
A
Transplant Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Monaco
A P
AP
Maki
T
T
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*
D000961:Antilymphocyte Serum; D020123:Sirolimus