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Author Notes:

Correspondence: Edmund K Waller, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, 1365B Clifton Rd. NE, Room B5119, Atlanta, GA, USA. Email: ewaller@emory.edu.

KAD and YW contributed equally.

KAD and YW designed and performed experiments, analyzed results and wrote the manuscript.

JML, WACH, and CRG designed and performed experiments.

CH performed experiments.

EKW designed experiments, analyzed results and wrote the manuscript.

All authors read and approved the final manuscript.

The authors declare that they have no competing interests.

Subject:

Keywords:

  • Interleukin-12
  • Engraftment
  • Transplantation
  • T-cells

Host bone marrow-derived IL-12 enhances donor T cell engraftment in a mouse model of bone marrow transplantation

Tools:

Journal Title:

Journal of Hematology & Oncology

Volume:

Volume 7, Number 16

Publisher:

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2014 Darlak et al.; licensee BioMed Central Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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