TY - JOUR
T1 - Graft invariant natural killer T-cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation
AU - Chaidos, Aristeidis
AU - Patterson, Scott
AU - Szydlo, Richard
AU - Chaudhry, Mohammed Suhail
AU - Dazzi, Francesco
AU - Kanfer, Edward
AU - McDonald, Donald
AU - Marin, David
AU - Milojkovic, Dragana
AU - Pavlu, Jiri
AU - Davis, John
AU - Rahemtulla, Amin
AU - Rezvani, Katy
AU - Goldman, John
AU - Roberts, Irene
AU - Apperley, Jane
AU - Karadimitris, Anastasios
PY - 2012/5/24
Y1 - 2012/5/24
N2 - 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 iNKTcell dose affects on the occurrence of clinically significant grade II-IV aGVHD in patients (n = 57) undergoing sibling, HLAidentical 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 of4.27 (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.
AB - 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 iNKTcell dose affects on the occurrence of clinically significant grade II-IV aGVHD in patients (n = 57) undergoing sibling, HLAidentical 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 of4.27 (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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U2 - 10.1182/blood-2011-11-389304
DO - 10.1182/blood-2011-11-389304
M3 - Article
C2 - 22371885
AN - SCOPUS:84860652954
SN - 0006-4971
VL - 119
SP - 5030
EP - 5036
JO - Blood
JF - Blood
IS - 21
ER -