Role of natural killer cell subsets in cardiac allograft rejection

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

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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 1

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Keywords

  • Costimulation
  • Mouse
  • NK cells
  • Tolerance
  • Transplantation

ASJC Scopus subject areas

  • Immunology

Cite this

McNerney, M. E., Lee, K-M., Zhou, P., Molinero, L., Mashayekhi, M., Guzior, D., Sattar, H., Kuppireddi, S., Wang, C. R., Kumar, V., & Alegre, M. L. (2006). Role of natural killer cell subsets in cardiac allograft rejection. American Journal of Transplantation, 6(3), 505-513. https://doi.org/10.1111/j.1600-6143.2005.01226.x