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

Research output: Contribution to journalArticle

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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

Fingerprint

Natural Killer Cells
Allografts
T-Lymphocytes
NK Cell Lectin-Like Receptor Subfamily K
Tissue Donors
Transplantation Tolerance
Immune Tolerance
Natural Killer T-Cells
Immunosuppressive Agents
Lymphocytes
Transplants
Pharmaceutical Preparations
Therapeutics

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., ... 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

Role of natural killer cell subsets in cardiac allograft rejection. / McNerney, M. E.; Lee, Kyung-Mi; Zhou, P.; Molinero, L.; Mashayekhi, M.; Guzior, D.; Sattar, H.; Kuppireddi, S.; Wang, C. R.; Kumar, V.; Alegre, M. L.

In: American Journal of Transplantation, Vol. 6, No. 3, 01.03.2006, p. 505-513.

Research output: Contribution to journalArticle

McNerney, ME, Lee, K-M, Zhou, P, Molinero, L, Mashayekhi, M, Guzior, D, Sattar, H, Kuppireddi, S, Wang, CR, Kumar, V & Alegre, ML 2006, 'Role of natural killer cell subsets in cardiac allograft rejection', American Journal of Transplantation, vol. 6, no. 3, pp. 505-513. https://doi.org/10.1111/j.1600-6143.2005.01226.x
McNerney, M. E. ; Lee, Kyung-Mi ; Zhou, P. ; Molinero, L. ; Mashayekhi, M. ; Guzior, D. ; Sattar, H. ; Kuppireddi, S. ; Wang, C. R. ; Kumar, V. ; Alegre, M. L. / Role of natural killer cell subsets in cardiac allograft rejection. In: American Journal of Transplantation. 2006 ; Vol. 6, No. 3. pp. 505-513.
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