Disparate role of LIGHT in organ-specific donor T cells activation and effector molecules in MHC class II disparate GVHD.

摘要

BACKGROUND: The present studies determined the role of LIGHT on organ-specific cytokine and effector molecules in acute graft-versus-host disease. METHODS: Cytokine and effector molecules were assessed by flow cytometry and quantitative PCR. RESULTS: More CD4+ spleen cells (SpC) expressing interferon-gamma (IFNgamma) and interleukin-2 were noted in SpC isolated from lethally irradiated bm12 X B6 F1 recipients of B6 donor SpC and T cell-depleted bone marrow cells and control Adv-betagal than in transplant (bone marrow transplantation (BMT)) recipients who had received Adv-LTbetaR-Ig or Adv-herpes simplex virus entry mediator (HVEM)-Ig. IFNgamma RNA levels from SpC, small intestines, and large intestines of control BMT recipients were significantly higher than those who had received Adv-HVEM-Ig. Granzyme B levels from SpC and small intestines of control BMT recipients were significantly higher than those that had received the Adv-LTbetaR-Ig. In contrast, BMT recipients of Adv-HVEM-Ig had lower granzyme A levels than controls in their large intestines. DISCUSSION: LIGHT inhibition differentially affects cytokines and effector molecules in SpC, small intestines, and large intestines, implicating different organ-specific pathways.