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Preemptive donor apoptotic cell infusions induce IFN-γ-producing myeloid-derived suppressor cells for cardiac allograft protection.

Publication ,  Journal Article
Bryant, J; Lerret, NM; Wang, J-J; Kang, H-K; Tasch, J; Zhang, Z; Luo, X
Published in: J Immunol
June 15, 2014

We have previously shown that preemptive infusion of apoptotic donor splenocytes treated with the chemical cross-linker ethylcarbodiimide (ECDI-SPs) induces long-term allograft survival in full MHC-mismatched models of allogeneic islet and cardiac transplantation. The role of myeloid-derived suppressor cells (MDSCs) in the graft protection provided by ECDI-SPs is unclear. In this study, we demonstrate that infusions of ECDI-SPs increase two populations of CD11b(+) cells in the spleen that phenotypically resemble monocytic-like (CD11b(+)Ly6C(high)) and granulocytic-like (CD11b(+)Gr1(high)) MDSCs. Both populations suppress T cell proliferation in vitro and traffic to the cardiac allografts in vivo to mediate their protection via inhibition of local CD8 T cell accumulation and potentially also via induction and homing of regulatory T cells. Importantly, repeated treatments with ECDI-SPs induce the CD11b(+)Gr1(high) cells to produce a high level of IFN-γ and to exhibit an enhanced responsiveness to IFN-γ by expressing higher levels of downstream effector molecules ido and nos2. Consequently, neutralization of IFN-γ completely abolishes the suppressive capacity of this population. We conclude that donor ECDI-SPs induce the expansion of two populations of MDSCs important for allograft protection mediated in part by intrinsic IFN-γ-dependent mechanisms. This form of preemptive donor apoptotic cell infusions has significant potential for the therapeutic manipulation of MDSCs for transplant tolerance induction.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

June 15, 2014

Volume

192

Issue

12

Start / End Page

6092 / 6101

Location

United States

Related Subject Headings

  • Spleen
  • Myeloid Cells
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Interferon-gamma
  • Immunology
  • Heart Transplantation
  • Graft Survival
  • Apoptosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bryant, J., Lerret, N. M., Wang, J.-J., Kang, H.-K., Tasch, J., Zhang, Z., & Luo, X. (2014). Preemptive donor apoptotic cell infusions induce IFN-γ-producing myeloid-derived suppressor cells for cardiac allograft protection. J Immunol, 192(12), 6092–6101. https://doi.org/10.4049/jimmunol.1302771

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

June 15, 2014

Volume

192

Issue

12

Start / End Page

6092 / 6101

Location

United States

Related Subject Headings

  • Spleen
  • Myeloid Cells
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Interferon-gamma
  • Immunology
  • Heart Transplantation
  • Graft Survival
  • Apoptosis