title: Allogeneic bone marrow grafts with high levels of CD4(+) CD25(+) FoxP3(+)  T cells can lead to engraftment failure.
abstract: Regulatory CD4(+) CD25(+) FoxP3(+) T cells (T(regs) ) suppress immunological reactions. However, the effect of adding T(regs) to hematopoietic stem cell grafts on recovery and graft versus host disease (GvHD) is unknown. T(regs) from splenocytes of C57Bl/6 and Balb/c wild-type mice were isolated by MACS separation and analyzed by flow cytometry. Using a murine syngeneic transplantation model that clearly distinguishes between donor and host hematopoiesis, we showed that co-transplantation of bone marrow cells (BMCs) with high levels of T(regs) leads to a 100% survival of the mice and accelerates the hematopoietic recovery significantly (full donor chimerism). In allogeneic transplantation, bone marrow and T(regs) co-transplantation were compared to allogeneic bone marrow transplantation with or without the addition of splenocytes. Survival, leukocyte recovery, chimerism at days -2, 19, 33, and 61 for murine CD4, human CD4, HLA-DR3, murine CD3, murine CD8, murine Balb/c-H2K(d) , murine C57Bl/6-H2K(b) , and GvHD appearance were analyzed. Allogeneic bone marrow transplantation requires the addition of splenocytes to reach engraftment. Mice receiving grafts with bone marrow, splenocytes and high levels of allogeneic T(regs) died within 28 days (hematopoietic failure). Here, we show also detailed flow cytometric data reagarding analysis of chimerism after transplantation in unique murine hematopoietic stem cell transplantation models. Our findings showed that the syngeneic co-transplantation of CD4(+) , CD25(+) , FoxP3(+) T-cells and BMCs induced a stimulating effect on reconstitution of hematopoiesis after irradiation. However, in the allogeneic setting the co-transplantation of T(regs) aggravates the engraftment of transplanted cells.
authors.affiliation: Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany. stephan.fricke@izi.fraunhofer.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Fricke
authors.forename: Katherina
authors.initials: K
authors.lastname: Rothe
authors.forename: Nadja
authors.initials: N
authors.lastname: Hilger
authors.forename: M
authors.initials: M
authors.lastname: Ackermann
authors.forename: Christopher
authors.initials: C
authors.lastname: Oelkrug
authors.forename: Christian
authors.initials: C
authors.lastname: Fricke
authors.forename: Uta
authors.initials: U
authors.lastname: Schönfelder
authors.forename: Dietger
authors.initials: D
authors.lastname: Niederwieser
authors.forename: Frank
authors.initials: F
authors.lastname: Emmrich
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sack
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D046528:Chimerism; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014185:Transplantation, Isogeneic; D017211:Treatment Failure; D014916:Whole-Body Irradiation