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Graft invariant natural killer T-cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.

Authors
  • Chaidos, Aristeidis
  • Patterson, Scott
  • Szydlo, Richard
  • Chaudhry, Mohammed Suhail
  • Dazzi, Francesco
  • Kanfer, Edward
  • McDonald, Donald
  • Marin, David
  • Milojkovic, Dragana
  • Pavlu, Jiri
  • Davis, John
  • Rahemtulla, Amin
  • Rezvani, Katy
  • Goldman, John
  • Roberts, Irene
  • Apperley, Jane
  • Karadimitris, Anastasios
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
May 24, 2012
Volume
119
Issue
21
Pages
5030–5036
Identifiers
DOI: 10.1182/blood-2011-11-389304
PMID: 22371885
Source
Medline
License
Unknown

Abstract

Invariant natural killer T (iNKT) cells are powerful immunomodulatory cells that in mice regulate a variety of immune responses, including acute GVHD (aGVHD). However, their clinical relevance and in particular their role in clinical aGVHD are not known. We studied whether peripheral blood stem cell (PBSC) graft iNKT-cell dose affects on the occurrence of clinically significant grade II-IV aGVHD in patients (n = 57) undergoing sibling, HLA-identical allogeneic HSCT. In multivariate analysis, CD4(-) iNKT-cell dose was the only graft parameter to predict clinically significant aGVHD. The cumulative incidence of grade II-IV aGVHD in patients receiving CD4(-) iNKT-cell doses above and below the median were 24.2% and 71.4%, respectively (P = .0008); low CD4(-) iNKT-cell dose was associated with a relative risk of grade II-IV aGVHD of 4.27 (P = .0023; 95% CI, 1.68-10.85). Consistent with a role of iNKT cells in regulating aGVHD, in mixed lymphocyte reaction assays, CD4(-) iNKT cells effectively suppressed T-cell proliferation and IFN-γ secretion in a contact-dependent manner. In conclusion, higher doses of CD4(-) iNKT cells in PBSC grafts are associated with protection from aGVHD. This effect could be harnessed for prevention of aGVHD.

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