[Study on control of graft-versus-host disease by blocking CD137-CD137L ligand costimulatory pathway in mice].
OBJECTIVE
To explore the in vitro effect on control of graft-versus-host disease (GVHD) and its mechanism in mice by blockade of CD137-CD137L pathway.


METHODS
Responder spleen cells from BALB/c donor mice (H-2(d)) were incubated with stimulator spleen cells from C57BL/6 ( H-2(b)) recipient mice, with or without anti-CD137L mAb. Lethally irradiated C57BL/6 mice were transplanted with donor bone marrow cells plus primary MLC spleen T cells. Group A (Allo-BMT control group): allo-BMT mice not receiving any prevention measures for GVHD. Group B (CsA + MTX control group): CsA and MTX given to C57BL/6 mice after transplantation. Group C (experimental group): donor spleen cells from BALB/c mice treated with anti-CD137L mAb. The percentages of CD3+ CD8+ T and CD3+ CD4+ T cells in the three groups were detected by flow cytometry, and the level of cytokines (IFN-gamma, IL-2, IL-10, IL-4) by RT-PCR.


RESULTS
The incidence of GVHD in group C was 70%, while in group A and group B were 100%. The survival rate was higher and the median survival time was longer of group C than that of group A and B (P < 0.01). All mice in group A died of aGVHD within 15 ds, while 30% of mice in group C survived more than 30 ds. Symptoms and histological signs of GVHD in group C were the mildest among the three groups. The percentage of CD3+ CD8+ T cells and the levels of IFN-gamma were significantly lower (P < 0.01), and the levels of IL-10 were significantly higher in group C than those in group A and B (P < 0.01).


CONCLUSIONS
Treatment of donor T cells with anti-CD137L mAb in vitro may relieve GVHD, thereby improve the survival time and survival rate, which maybe related to increasing Th1 cytokine (IFN-gamma) and decreasing Th2 cytokine (IL-10) as well as reducing CD3+ CD8+ T cells.
Li
Chao-Hong
CH
The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. lrhmd@163.com
Xu
Kai-Lin
KL
Pan
Xiu-Ying
XY
Du
Bing
B
D053330:4-1BB Ligand / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D016026:Bone Marrow Transplantation / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology*
D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9