title: Depletion of alloantigen-primed lymphocytes overcomes resistance to allogeneic bone marrow in mildly conditioned recipients.
abstract: OBJECTIVE
  Successful implantation of allogeneic bone marrow (BM) cells after nonmyeloablative conditioning would allow to compensate for the inadequate supply of compatible grafts and to reduce mortality of graft-vs.-host disease (GVHD). Recently, we proposed to facilitate engraftment of mismatched BM by conditioning for alloantigen-primed lymphocyte depletion (APLD) with cyclophosphamide (CY). Here we summarize the experimental results obtained by this approach.
  
  
  METHODS
  Naive or mildly irradiated BALB/c mice were primed with C57BL/6 BM cells (day 0), treated with CY (day 1) to deplete alloantigen-primed lymphocytes, and given a second C57BL/6 BM transplant (day 2) for engraftment. Recipients were repeatedly tested for chimerism in the blood and followed for GVHD and survival. The protocol was also tested for inducing tolerance to donor tissue and organ allografts, and for treatment of leukemia, breast cancer, and autoimmune diabetes in NOD mice.
  
  
  RESULTS
  APLD by 200 mg/kg CY provided engraftment of allogeneic BM from the same donor in 100% mildly irradiated recipients. Eighty percent chimeras remained GVHD-free more 200 days. All chimeras accepted permanently donor skin grafts and donor hematopoietic stromal progenitors. Allogeneic BM transplantation (BMT) after APLD had a strong therapeutic potential in BALB/c mice harboring malignant cells and in autoimmune NOD recipients. Tolerance-inducing CY dose could be reduced to 100 mg/kg. Conditioning for APLD resulted in engraftment of allogeneic BM after a significantly lower radiation dose than treatment with radiation and CY alone.
  
  
  CONCLUSIONS
  Our results demonstrate that conditioning for APLD has a definite advantage over general immunosuppression with CY and radiation therapy.
authors.affiliation: Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Tatyana B
authors.initials: TB
authors.lastname: Prigozhina
authors.forename: Gregory
authors.initials: G
authors.lastname: Elkin
authors.forename: Olga
authors.initials: O
authors.lastname: Gurevitch
authors.forename: Shoshana
authors.initials: S
authors.lastname: Morecki
authors.forename: Elena
authors.initials: E
authors.lastname: Yakovlev
authors.forename: Sofia
authors.initials: S
authors.lastname: Khitrin
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D016026:Bone Marrow Transplantation; D006085:Graft Survival / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous