Study of Relieving Graft-versus-Host Disease by Blocking CD137-CD137 Ligand Costimulatory Pathway in Vitro Authors
Received: 10 July 2006 Revised: 04 April 2007 Accepted: 26 April 2007 DOI:
Cite this article as: Xu, K., Li, C., Pan, X. et al. Int J Hematol (2007) 86: 84. doi:10.1532/IJH97.A10613 Abstract
Engagement of the TCR without appropriate costimulation will result in the inability of T-cells to respond to the alloantigen as described earlier. We made a further investigation into the effect of relieving graft-versus-host disease (GVHD) and its mechanism in mice by blocking CD137-CD137L pathway in vitro. Responder cells (spleen cells) from BALB/C donor mice (H-2
d) were incubated with stimulator cells (spleen cells) from C57BL/6 recipient mice (H-2 b),with or without anti-CD137L monoclonal antibodies (MoAbs). Donor bone marrow cells plus mixed lymphocyte culture (MLC) T-cells were transplanted into lethally irradiated C57BL/6 mice. C57BL/6 mice were divided into 3 groups: group A (allogeneic bone marrow transplantation control group), group B (cyclosporine + methotrexate group), and group C (donor T-cells were treated with anti-CD137L MoAbs). The percentage of CD 3+CD 4+ and CD 3+CD 8+ T-cells were detected by flow cytometry, and the levels of cytokines (IFN-γ, interleukin [IL]-2, IL-10, IL-4) by reverse-transcriptase polymerase chain reaction.The incidence of GVHD in group C was 70%, while the incidence of GVHD was 100% in group A and group B. The survival rate of group C was higher than that of group A and B, and the median survival time was longer than that of group A and B (P < .01). Clinical symptoms and histological signs of GVHD in group C were the mildest among all 3 groups. The percentage of CD 3 +CD 8 + T-cells in group C was lower than that in group A and B (P < .01). The levels of IFN-γ in group C were markedly lower than those in group A and B (P < .01), and the levels of IL-10 in group C were significantly higher than those in group A and B (P < .01).The results suggest that treatment of donor T-cells by anti-CD137L MoAbs in vitro may relieve GVHD, thereby improve the survival time and survival rate of recipient mice, which might be related to the increased TH1 cytokine (IFN-γ) and decreased TH2 cytokine (IL-10) as well as the reduced CD 3 +CD 8 + T-cells. Key words Bone marrow transplantation Graft-versus-host disease Anti-CD137L MoAbs Immune tolerance References
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