Adoptive therapy by transfusing expanded donor murine natural killer T cells can suppress acute graft-versus-host disease in allogeneic bone marrow 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).


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.


CONCLUSIONS
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.
Yang
Jie
J
Blood Engineering Laboratory, Shanghai Blood Center, Shanghai, China.
Gao
Li
L
Liu
Yan
Y
Ren
Yana
Y
Xie
Rufeng
R
Fan
Huahua
H
Qian
Kaicheng
K
D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D005699:Galactosylceramides / Q000494:pharmacology; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy*; D006200:Hair Color; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000502:physiology; D015848:Interleukin-5 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000276:immunology
D005699:Galactosylceramides; D007376:Interleukin-2; D015848:Interleukin-5; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma