MHC-Mismatched Murine Committed Myeloid Progenitors Engraft and Protect Against Invasive Aspergillosis. Session Type: Poster Session 724-III

Caroline Arber, Andrew BitMansour, Janice M. Brown

Author address: 

Medicine/ Bone Marrow Transplantation and Infectious Diseases, Stanford University, Stanford, CA, USA

Abstract: 

Transplantation of grafts containing both congenic bone marrow derived committed myeloid progenitors common myeloid progenitors (CMPs) and granulocyte monocyte progenitors (GMPs) and hematopoietic stem cells (HSCs) after myeloablative treatment protect against invasive aspergillosis that was lethal for mice that received grafts containing only HSCs (BitMansour et al, Blood, 2002;100(13):4660-7). Here, we demonstrate that allogeneic CMPs and GMPs from unrelated MHC-matched and MHC-mismatched donors not only engraft but also protect against lethal challenge with Aspergillus fumigatus. Donor HSCs were isolated by fluorescence-activated cell sorting from C57/BL6.CD45.2.Thy1.1 (H2b) mice (MHC-matched model) or B10.D2.CD45.2.Thy1.1 (H2d) mice (MHC-mismatched model). For both models, CMPs and GMPs were isolated from C57/BL6.CD45.1 mice and transplanted either into lethally irradiated BALB.B (H2b, MHC-matched) or Balb/c (H2d, MHC-mismatched) recipients. On day 7 post-transplantation, mice were challenged with 100 conidia A. fumigatus intravenously. Mice co-transplanted with 10000 CMPs and 20000 GMPs from MHC-matched donors survived infection compared to mice transplanted with HSCs alone that succumbed to invasive aspergillosis (n=10 each group, survival 90 % versus 40%). Similar results were obtained in the MHC-mismatched model where mice co-transplanted with the same number of CMPs and GMPs were protected against invasive aspergillosis when compared to mice transplanted with HSCs alone (n=10 each group, survival 70% versus 20%). CMP/ GMP-derived cells were detected in spleen and bone marrow on day 7 post-transplantation but were undetectable by day 28 post-transplantation. Absolute numbers of progenitor-derived cells in the spleen were comparable regardless of whether the donor was congenic or MHC-matched to the host. In contrast, a significantly lower number of progenitor-derived splenocytes resulted following MHC-mismatched transplantation, confirming that protection against A. fumigatus can be achieved with modest augmentation of cell populations. Thus, transplantation of purified committed myeloid progenitors protect against invasive aspergillosis after HSC transplantation in congenic, unrelated MHC-matched, and MHC-mismatched murine recipients. These data suggest that the human counterpart of these progenitors may have a broader range of applicability as adjunctive treatment to decrease susceptibility to fungal infections during neutropenia. Abstract #3504 appears in Blood, Volume 102, issue 11, November 16, 2003
2003

abstract No: 

3504

Full conference title: 

American Society of Hematology 45th Annual Meeting
    • ASH 45th (2003)