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


CONCLUSIONS
LIGHT inhibition differentially affects cytokines and effector molecules in SpC, small intestines, and large intestines, implicating different organ-specific pathways.
Brown
Geri R
GR
Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. geri.brown@utsouthwestern.edu
Lane
George W
GW
Whittington
Bonnie J
BJ
D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006086:Graft vs Host Disease; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007420:Intestine, Large / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009928:Organ Specificity; D015202:Protein Engineering; D011828:Radiation Chimera; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14