Role of natural killer cell subsets in cardiac allograft rejection

M. E. McNerney, K. M. Lee, P. Zhou, L. Molinero, M. Mashayekhi, D. Guzior, H. Sattar, S. Kuppireddi, C. R. Wang, V. Kumar, M. L. Alegre

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4+ T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8 + T cells and NK1.1+ cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2 + NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.

Original languageEnglish
Pages (from-to)505-513
Number of pages9
JournalAmerican Journal of Transplantation
Volume6
Issue number3
DOIs
Publication statusPublished - 2006 Mar

Keywords

  • Costimulation
  • Mouse
  • NK cells
  • Tolerance
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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