Functional Reconstitution of Natural Killer Cells in Allogeneic Hematopoietic Stem Cell Transplantation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2016 May 6

PMID 27148263

Citations 58

Authors

Md Ashik Ullah

Geoffrey R Hill

Siok-Keen Tey

Affiliations

Soon will be listed here.

Abstract

Natural killer (NK) cells are the first lymphocyte population to reconstitute following allogeneic hematopoietic stem cell transplantation (HSCT) and are important in mediating immunity against both leukemia and pathogens. Although NK cell numbers generally reconstitute within a month, the acquisition of mature NK cell phenotype and full functional competency can take 6 months or more, and is influenced by graft composition, concurrent pharmacologic immunosuppression, graft-versus-host disease, and other clinical factors. In addition, cytomegalovirus infection and reactivation have a dominant effect on NK cell memory imprinting following allogeneic HSCT just as it does in healthy individuals. Our understanding of NK cell education and licensing has evolved in the years since the "missing self" hypothesis for NK-mediated graft-versus-leukemia effect was first put forward. For example, we now know that NK cell "re-education" can occur, and that unlicensed NK cells can be more protective than licensed NK cells in certain settings, thus raising new questions about how best to harness graft-versus-leukemia effect. Here, we review current understanding of the functional reconstitution of NK cells and NK cell education following allogeneic HSCT, highlighting a conceptual framework for future research.

Citing Articles

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References

Lang I, Gunn H, Lydyard P . Effect of in vitro cyclosporin. A treatment on human natural and antibody-dependent cell-mediated cytotoxicity. Transplantation. 1983; 35(2):127-9. DOI: 10.1097/00007890-198302000-00004. View

Bjorklund A, Schaffer M, Fauriat C, Ringden O, Remberger M, Hammarstedt C . NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLA-matched sibling stem cell transplantation. Blood. 2010; 115(13):2686-94. PMC: 2852367. DOI: 10.1182/blood-2009-07-229740. View

Fehniger T, Cooper M, Nuovo G, Cella M, Facchetti F, Colonna M . CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood. 2002; 101(8):3052-7. DOI: 10.1182/blood-2002-09-2876. View

Lopez-Verges S, Milush J, Schwartz B, Pando M, Jarjoura J, York V . Expansion of a unique CD57⁺NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci U S A. 2011; 108(36):14725-32. PMC: 3169160. DOI: 10.1073/pnas.1110900108. View

Lazarevic V, Glimcher L . T-bet in disease. Nat Immunol. 2011; 12(7):597-606. PMC: 6290474. DOI: 10.1038/ni.2059. View

Elmaagacli A, Steckel N, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski M . Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients. Blood. 2011; 118(5):1402-12. DOI: 10.1182/blood-2010-08-304121. View

Yamasaki S, Henzan H, Ohno Y, Yamanaka T, Iino T, Itou Y . Influence of transplanted dose of CD56+ cells on development of graft-versus-host disease in patients receiving G-CSF-mobilized peripheral blood progenitor cells from HLA-identical sibling donors. Bone Marrow Transplant. 2003; 32(5):505-10. DOI: 10.1038/sj.bmt.1704165. View

Velardi A . Natural killer cell alloreactivity 10 years later. Curr Opin Hematol. 2012; 19(6):421-6. DOI: 10.1097/MOH.0b013e3283590395. View

Dulphy N, Haas P, Busson M, Belhadj S, Peffault de Latour R, Robin M . An unusual CD56(bright) CD16(low) NK cell subset dominates the early posttransplant period following HLA-matched hematopoietic stem cell transplantation. J Immunol. 2008; 181(3):2227-37. DOI: 10.4049/jimmunol.181.3.2227. View

10.

Munneke J, Bjorklund A, Mjosberg J, Garming-Legert K, Bernink J, Blom B . Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. Blood. 2014; 124(5):812-21. DOI: 10.1182/blood-2013-11-536888. View

11.

Simonetta F, Pradier A, Bosshard C, Masouridi-Levrat S, Chalandon Y, Roosnek E . NK Cell Functional Impairment after Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Reduced Levels of T-bet and Eomesodermin. J Immunol. 2015; 195(10):4712-20. DOI: 10.4049/jimmunol.1501522. View

12.

Suessmuth Y, Mukherjee R, Watkins B, Koura D, Finstermeier K, Desmarais C . CMV reactivation drives posttransplant T-cell reconstitution and results in defects in the underlying TCRβ repertoire. Blood. 2015; 125(25):3835-50. PMC: 4473113. DOI: 10.1182/blood-2015-03-631853. View

13.

Vivier E, Ugolini S . Natural killer cells: from basic research to treatments. Front Immunol. 2012; 2:18. PMC: 3342003. DOI: 10.3389/fimmu.2011.00018. View

14.

Shenoy S, Mohanakumar T, Todd G, Westhoff W, Dunnigan K, Adkins D . Immune reconstitution following allogeneic peripheral blood stem cell transplants. Bone Marrow Transplant. 1999; 23(4):335-46. DOI: 10.1038/sj.bmt.1701581. View

15.

Orr M, Lanier L . Natural killer cell education and tolerance. Cell. 2010; 142(6):847-56. PMC: 2945212. DOI: 10.1016/j.cell.2010.08.031. View

16.

Bjorkstrom N, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson M . Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood. 2010; 116(19):3853-64. DOI: 10.1182/blood-2010-04-281675. View

17.

Wang H, Grzywacz B, Sukovich D, McCullar V, Cao Q, Lee A . The unexpected effect of cyclosporin A on CD56+CD16- and CD56+CD16+ natural killer cell subpopulations. Blood. 2007; 110(5):1530-9. PMC: 1975839. DOI: 10.1182/blood-2006-10-048173. View

18.

Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M . Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood. 2004; 104(12):3664-71. DOI: 10.1182/blood-2004-05-2058. View

19.

Ottinger H, Beelen D, Scheulen B, Schaefer U, Grosse-Wilde H . Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow. Blood. 1996; 88(7):2775-9. View

20.

Abrahamsen I, Somme S, Heldal D, Egeland T, Kvale D, Tjonnfjord G . Immune reconstitution after allogeneic stem cell transplantation: the impact of stem cell source and graft-versus-host disease. Haematologica. 2005; 90(1):86-93. View