Kinetics of Th1 and Th2 cytokine production during the early course of acute and chronic murine graft-versus-host disease. Regulatory role of donor CD8+ T cells
- PMID: 7650373
Kinetics of Th1 and Th2 cytokine production during the early course of acute and chronic murine graft-versus-host disease. Regulatory role of donor CD8+ T cells
Abstract
Acute and chronic graft-versus-host disease (GVHD) in the parent-into-F1 model are mediated by predominantly cellular or humoral immune responses, respectively, and are strikingly different entities by 2 wk of disease. Both forms of GVHD, however, evolve from a common starting point, i.e., donor CD4+ T cell recognition of host alloantigen and IL-2 production. Our study examines the first 2 wk of GVHD to delineate the events that critically influence GVHD development. Surprisingly, both forms of GVHD are initially characterized by increased Th2 cytokine (IL-4 and IL-10) production and B cell activation which persists into wk 2. The earliest distinguishing features of acute GVHD were detectable at days 5 through 7 of disease and consisted of 1) expansion of donor CD8+ T cells, and 2) increased IFN-gamma production by donor CD4+ and CD8+ T cells. Interestingly, IFN-gamma production by donor CD4+ T cells was not seen if donor CD8+ T cells were not engrafted in comparable numbers. Chronic GVHD in the DBA-into-BDF1 model was found to be caused by a relative defect in the ability of DBA CD8+ T cells to induce acute GVHD and to produce IFN-gamma. These studies demonstrate that both acute and chronic GVHD begin as a Th2 cytokine-mediated, B cell stimulatory response. The transition to acute GVHD is critically dependent on the engraftment of donor CD8+ T cells, which terminate B cell hyperactivity by 1) eliminating activated B cells and 2) promoting IFN-gamma secretion by donor CD4+ T cells.
Similar articles
-
Differential expression of Fas and Fas ligand in acute and chronic graft-versus-host disease: up-regulation of Fas and Fas ligand requires CD8+ T cell activation and IFN-gamma production.J Immunol. 1998 Sep 15;161(6):2848-55. J Immunol. 1998. PMID: 9743345
-
The flavonoid Kaempferol suppresses the graft-versus-host reaction by inhibiting type 1 cytokine production and CD8+ T cell engraftment.Clin Immunol. 2002 May;103(2):132-44. doi: 10.1006/clim.2001.5187. Clin Immunol. 2002. PMID: 12027418
-
Neutralizing IL-12 during induction of murine acute graft-versus-host disease polarizes the cytokine profile toward a Th2-type alloimmune response and confers long term protection from disease.J Immunol. 1997 Aug 1;159(3):1208-15. J Immunol. 1997. PMID: 9233615
-
[A role for T-helper type 1 and type 2 cytokines in the pathogenesis of various human diseases].Rinsho Byori. 1998 Sep;46(9):915-21. Rinsho Byori. 1998. PMID: 9800477 Review. Japanese.
-
The role of cytokines in graft-versus-host reactions and disease.Bone Marrow Transplant. 1992 Jul;10(1):1-14. Bone Marrow Transplant. 1992. PMID: 1515873 Review.
Cited by
-
Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity.J Clin Invest. 2000 Sep;106(6):R39-47. doi: 10.1172/JCI8876. J Clin Invest. 2000. PMID: 10995792 Free PMC article.
-
Recent advances in the treatment of graft-versus-host disease.Clin Med Res. 2004 Nov;2(4):243-52. doi: 10.3121/cmr.2.4.243. Clin Med Res. 2004. PMID: 15931364 Free PMC article. Review.
-
Suppression of Murine Lupus by CD4+ and CD8+ Treg Cells Induced by T Cell-Targeted Nanoparticles Loaded With Interleukin-2 and Transforming Growth Factor β.Arthritis Rheumatol. 2019 Apr;71(4):632-640. doi: 10.1002/art.40773. Epub 2019 Mar 5. Arthritis Rheumatol. 2019. PMID: 30407752 Free PMC article.
-
The complex and central role of interferon-γ in graft-versus-host disease and graft-versus-tumor activity.Immunol Rev. 2014 Mar;258(1):30-44. doi: 10.1111/imr.12151. Immunol Rev. 2014. PMID: 24517424 Free PMC article. Review.
-
IL-21 promotes lupus-like disease in chronic graft-versus-host disease through both CD4 T cell- and B cell-intrinsic mechanisms.J Immunol. 2012 Jul 15;189(2):1081-93. doi: 10.4049/jimmunol.1200318. Epub 2012 Jun 20. J Immunol. 2012. PMID: 22723520 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Other Literature Sources
Research Materials