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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.

Original publication

DOI

10.1182/blood-2011-11-389304

Type

Journal article

Journal

Blood

Publication Date

24/05/2012

Volume

119

Pages

5030 - 5036

Keywords

Adult, Aged, Directed Tissue Donation, Female, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing, Humans, Incidence, Lymphocyte Count, Male, Middle Aged, Natural Killer T-Cells, Prognosis, Risk Factors, Siblings, Tissue Donors, Transplantation Immunology, Transplantation, Homologous