Alleviation of acute and chronic graft-versus-host disease in a murine model is associated with glucocerebroside-enhanced natural killer T lymphocyte plasticity.
BACKGROUND
Natural killer T (NKT) lymphocytes play a role in graft-versus-host disease GVHD (GVHD). Glucocerebroside (GC) is a naturally occurring glycolipid that plays a role in the immune modulation of NKT lymphocytes. This study aims to determine the effect of GC in murine models of semiallogeneic/acute and chronic GVHD.


METHODS
Acute and chronic GVHD were generated by fusion of splenocytes from C57BL/6 to (C57BL/6xBalb/c) F1 mice, and from B10.D2 donor mice into Balb/c, respectively. Recipients were treated daily with GC. Histological and immunological parameters of GVHD were assessed.


RESULTS
Treatment with GC significantly alleviated GVHD in both models The beneficial effect of GC was associated with an increase in the intrahepatic/peripheral NKT lymphocyte ratio in the semiallogeneic/acute model. This ratio was decreased in the chronic GVHD model. A significant increase in intrahepatic CD8+ lymphocyte trapping was noted in the semiallogeneic/acute model, whereas the opposite effect was observed in the chronic GVHD model. Administration of GC led to decreased serum interferon-gamma and increased serum interleukin-4 levels in the Th1-mediated model, whereas the opposite effect was observed in the Th2-mediated models.


CONCLUSIONS
GC ameliorates GVHD in both Th1- and Th2-mediated murine models, suggesting it is able to differentially affect the immune system. GC may alleviate immunologically incongruous disorders, and may be associated with "fine tuning" of immune responses.
Ilan
Yaron
Y
Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. ilan@hadassah.org.il
Ohana
Meir
M
Pappo
Orit
O
Margalit
Maya
M
Lalazar
Gadi
G
Engelhardt
Dean
D
Rabbani
Elazar
E
Nagler
Arnon
A
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement; D002908:Chronic Disease; D004195:Disease Models, Animal; D005963:Glucosylceramides / Q000494:pharmacology*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D014184:Transplantation, Homologous
D005963:Glucosylceramides