title: Host bone marrow-derived IL-12 enhances donor T cell engraftment in a mouse model of bone marrow transplantation.
abstract: BACKGROUND
  Donor cell engraftment is critical for the success of allogeneic bone marrow transplants. Graft failure is a result of donor cells either failing to engraft initially or being eliminated at later time points. Donor cell engraftment is facilitated by donor T cells, which eliminate residual host hemato-lymphoid effector cells such as NK cells and T cells.
  
  
  METHODS
  We aimed to explore the role of host hematopoietic cell derived IL-12 on donor cell engraftment in a murine model of BMT. We established radiation chimeras by transplanting C57BL6/J (B6) mice with BM from either congenic B6 mice or IL-12p40 KO mice. These WT → WT or IL-12 KO → WT chimeras then underwent a secondary transplant with allogeneic (FVB) BM. Survival, engraftment, donor T cell expansion, cytokine production by donor T cells, as well as expression of stimulatory markers on donor T cells was analyzed.
  
  
  RESULTS
  Mice whose residual host hematopoietic cells were capable of producing IL-12 had modestly higher survival, higher donor T cell engraftment, and significantly higher donor erythroid engraftment. We have also found that an increased number of donor T cells in IL-12 KO → WT chimeras have a regulatory phenotype, expressing FoxP3, producing lower levels of TNF-α, higher levels of IL-10, and expressing higher levels of ICOS as well as PD-1 on CD4+ T cells.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of a beneficial role of IL-12 production by host cells in the context of bone marrow engraftment in a murine model of BMT. These findings support the clinical use of exogenous IL-12 for use in settings where graft failure is of concern.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Darlak
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Li
authors.forename: Wayne Ac
authors.initials: WA
authors.lastname: Harris
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Giver
authors.forename: Chunzi
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, 1365B Clifton Rd, NE, Room B5119, Atlanta, GA, USA. ewaller@emory.edu.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000637:transplantation*; D014019:Tissue Donors
chemical_list: D018664:Interleukin-12