title: Graft invariant natural killer T-cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.
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.
authors.affiliation: Centre for Haematology, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Aristeidis
authors.initials: A
authors.lastname: Chaidos
authors.forename: Scott
authors.initials: S
authors.lastname: Patterson
authors.forename: Richard
authors.initials: R
authors.lastname: Szydlo
authors.forename: Mohammed Suhail
authors.initials: MS
authors.lastname: Chaudhry
authors.forename: Francesco
authors.initials: F
authors.lastname: Dazzi
authors.forename: Edward
authors.initials: E
authors.lastname: Kanfer
authors.forename: Donald
authors.initials: D
authors.lastname: McDonald
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.forename: Dragana
authors.initials: D
authors.lastname: Milojkovic
authors.forename: Jiri
authors.initials: J
authors.lastname: Pavlu
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.forename: Amin
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: Katy
authors.initials: K
authors.lastname: Rezvani
authors.forename: John
authors.initials: J
authors.lastname: Goldman
authors.forename: Irene
authors.initials: I
authors.lastname: Roberts
authors.forename: Jane
authors.initials: J
authors.lastname: Apperley
authors.forename: Anastasios
authors.initials: A
authors.lastname: Karadimitris
mesh_terms: D000328:Adult; D000368:Aged; D033001:Directed Tissue Donation; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D019337:Hematologic Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000637:transplantation*; D011379:Prognosis; D012307:Risk Factors; D035781:Siblings; D014019:Tissue Donors; D014181:Transplantation Immunology / Q000276:immunology / Q000502:physiology; D014184:Transplantation, Homologous