Study on control of graft-versus-host disease by blocking CD137-CD137L ligand costimulatory pathway in mice / 中华血液学杂志
Chinese Journal of Hematology
; (12): 93-97, 2007.
Article
in Zh
| WPRIM
| ID: wpr-328368
Responsible library:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>
Full text:
1
Index:
WPRIM
Main subject:
Pharmacology
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Transplantation, Homologous
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Bone Marrow Transplantation
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Disease Models, Animal
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Allergy and Immunology
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4-1BB Ligand
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Graft vs Host Disease
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Mice, Inbred BALB C
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Mice, Inbred C57BL
Type of study:
Prognostic_studies
Limits:
Animals
Language:
Zh
Journal:
Chinese Journal of Hematology
Year:
2007
Type:
Article