NKG2D expression by CD8+ T cells contributes to GVHD and GVT effects in a murine model of allogeneic HSCT.

Blood
Mobin A KarimiTaku Kambayashi

Abstract

In allogeneic hematopoietic stem cell transplantation (HSCT), controlling graft-versus-host disease (GVHD) while maintaining graft-versus-tumor (GVT) responses is of critical importance. Using a mouse model of allogeneic HSCT, we hereby demonstrate that NKG2D expression by CD8(+) T cells plays a major role in mediating GVHD and GVT effects by promoting the survival and cytotoxic function of CD8(+) T cells. The expression of NKG2D ligands was not induced persistently on normal tissues of allogeneic HSCT-recipient mice treated with anti-NKG2D antibody, suggesting that transient NKG2D blockade might be sufficient to attenuate GVHD and allow CD8(+) T cells to regain their GVT function. Indeed, short-term treatment with anti-NKG2D antibody restored GVT effects while maintaining an attenuated GVHD state. NKG2D expression was also detected on CD8(+) T cells from allogeneic HSCT patients and trended to be higher in those with active GVHD. Together, these data support a novel role for NKG2D expression by CD8(+) T cells during allogeneic HSCT, which could be potentially therapeutically exploited to separate GVHD from GVT effects.

References

Jan 1, 1989·Advances in Immunology·G Trinchieri
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·V GrohT Spies
Jun 3, 1999·The New England Journal of Medicine·E C GuinanJ G Gribben
Mar 22, 2002·Nature Reviews. Immunology·M L AlegreC B Thompson
Jul 3, 2002·Nature Reviews. Immunology·Alan G Baxter, Philip D Hodgkin
Jul 16, 2002·Annual Review of Biomedical Engineering·Christopher H Contag, Michael H Bachmann
Oct 3, 2003·Nature Reviews. Immunology·David H Raulet
Jun 11, 2004·Immunity·Kouetsu OgasawaraLewis L Lanier
Apr 20, 2005·Journal of Immunotherapy·Loredana RuggeriAndrea Velardi
May 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·David GarrityKai W Wucherpfennig
Jun 7, 2005·Advances in Experimental Medicine and Biology·Lewis L Lanier
Sep 15, 2005·British Journal of Haematology·Dimitri A Breems, Bob Löwenberg
Dec 13, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mobin KarimiRobert S Negrin
Apr 18, 2008·The European Respiratory Journal·K KraetzelC Schulz
Mar 14, 2009·Lancet·James L M FerraraErnst Holler
Sep 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Vincent T HoRobert Soiffer
Jan 10, 2013·Annual Review of Immunology·David H RauletHeiyoun Jung
Jun 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Felix M WensveenBojan Polic
Jul 17, 2013·Cell Research·Giulio Maria PasinettiWei Zhao
Nov 19, 2013·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·James L M Ferrara
Aug 6, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mobin A KarimiTaku Kambayashi

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Citations

Aug 23, 2017·Nature Communications·Satish RanjanBerend Isermann
Jun 4, 2019·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Dongdong YuShusen Zheng
Apr 12, 2017·Frontiers in Immunology·Raphael CarapitoSeiamak Bahram
Jul 17, 2020·Science Translational Medicine·Cameron S BaderRobert B Levy
May 22, 2020·JCI Insight·Hemn MohammadpourPhilip L McCarthy
Apr 22, 2020·Nature Reviews. Clinical Oncology·Bruce R BlazarWilliam J Murphy
Nov 22, 2016·Frontiers in Immunology·Branca I Pereira, Arne N Akbar
Dec 23, 2020·International Journal of Immunogenetics·Katarzyna Bogunia-Kubik, Piotr Łacina
Nov 11, 2018·Trends in Immunology·Sarah K WhitesideJanis J Weis

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