BACKGROUND: Invariant natural killer T cells (iNKT cells) may suppress graft-versus-host disease (GVHD) after allogeneic transplantation. The purpose of this study was to investigate the therapeutic potential of iNKT cells from major histocompatibility complex (MHC)-mismatched donors for preventing GVHD after allogeneic bone marrow transplantation (BMT). STUDY DESIGN AND METHODS: In vitro, mouse iNKT cells were expanded with alpha-galactosylceramide and interleukin (IL)-2 treatment. In the NKT-treated group, lethally irradiated DBA/2(H-2K(d)) mice were adoptively transferred with expanded iNKT, bone marrow (BM), and spleen cells (SCs) from C57BL/6 (H-2K(b)) mice. Recipients in the control group were transferred only BM and SCs. The two groups were compared in survival, weight, histopathologic specimens, and serum cytokine analysis. RESULTS: In the iNKT-treated group, 80% of mice survived past Day 60 after BMT, but all died within 38 days in the control group. The mice treated with iNKT did not exhibit signs of GVHD after Day 42 except for a change in fur color. There were higher IL-4 levels by Day 7 in serum of mice that received iNKT compared to those without iNKT treatment, while the interferon-gamma levels showed no significant difference between two groups. Levels of IL-2 and IL-5 increased by Day 21 only in iNKT-treated mice. CONCLUSION: The results suggest that donor iNKT cells could alleviate GVHD symptoms and prolong survival after MHC-mismatched allogeneic BMT, which may be associated with the maintenance in IL-4 levels. These findings indicate that the therapy based on iNKT cells from MHC-mismatched donors has great potential in protection against GVHD after allogeneic hematopoietic stem cell transplantation.
BACKGROUND: Invariant natural killer T cells (iNKT cells) may suppress graft-versus-host disease (GVHD) after allogeneic transplantation. The purpose of this study was to investigate the therapeutic potential of iNKT cells from major histocompatibility complex (MHC)-mismatched donors for preventing GVHD after allogeneic bone marrow transplantation (BMT). STUDY DESIGN AND METHODS: In vitro, mouse iNKT cells were expanded with alpha-galactosylceramide and interleukin (IL)-2 treatment. In the NKT-treated group, lethally irradiated DBA/2(H-2K(d)) mice were adoptively transferred with expanded iNKT, bone marrow (BM), and spleen cells (SCs) from C57BL/6 (H-2K(b)) mice. Recipients in the control group were transferred only BM and SCs. The two groups were compared in survival, weight, histopathologic specimens, and serum cytokine analysis. RESULTS: In the iNKT-treated group, 80% of mice survived past Day 60 after BMT, but all died within 38 days in the control group. The mice treated with iNKT did not exhibit signs of GVHD after Day 42 except for a change in fur color. There were higher IL-4 levels by Day 7 in serum of mice that received iNKT compared to those without iNKT treatment, while the interferon-gamma levels showed no significant difference between two groups. Levels of IL-2 and IL-5 increased by Day 21 only in iNKT-treated mice. CONCLUSION: The results suggest that donor iNKT cells could alleviate GVHD symptoms and prolong survival after MHC-mismatched allogeneic BMT, which may be associated with the maintenance in IL-4 levels. These findings indicate that the therapy based on iNKT cells from MHC-mismatched donors has great potential in protection against GVHD after allogeneic hematopoietic stem cell transplantation.
Authors: Aristeidis Chaidos; Scott Patterson; Richard Szydlo; Mohammed Suhail Chaudhry; Francesco Dazzi; Edward Kanfer; Donald McDonald; David Marin; Dragana Milojkovic; Jiri Pavlu; John Davis; Amin Rahemtulla; Katy Rezvani; John Goldman; Irene Roberts; Jane Apperley; Anastasios Karadimitris Journal: Blood Date: 2012-02-27 Impact factor: 22.113
Authors: M-T Rubio; M Bouillié; N Bouazza; T Coman; H Trebeden-Nègre; A Gomez; F Suarez; D Sibon; A Brignier; E Paubelle; S Nguyen-Khoc; M Cavazzana; O Lantz; M Mohty; S Urien; O Hermine Journal: Leukemia Date: 2016-10-14 Impact factor: 11.528
Authors: Dennis B Leveson-Gower; Janelle A Olson; Emanuela I Sega; Richard H Luong; Jeanette Baker; Robert Zeiser; Robert S Negrin Journal: Blood Date: 2011-01-21 Impact factor: 22.113
Authors: Kelly Andrews; Anouk A J Hamers; Xiaodian Sun; Geoffrey Neale; Katherine Verbist; Paige Tedrick; Kim E Nichols; Shalini Pereira; Daniel E Geraghty; Asha B Pillai Journal: Cytotherapy Date: 2020-03-29 Impact factor: 5.414