1 / 24

Host

(I) Conditioning. Tissue Damage. Host. Small. tissues. intestine. LPS. TNF- a IL-1 LPS. f. M. APC. TNF- a IL-1. CD4 CTL. IFN- g. Donor. T Cell. Target cell apoptosis. (III). (II). CD8 CTL. Cellular and. Donor. TNF- a IL-1. inflammatory. T-cell. Th. 1. CD8 CTL.

miller
Download Presentation

Host

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. (I) Conditioning Tissue Damage Host Small tissues intestine LPS TNF-a IL-1 LPS f M APC TNF-a IL-1 CD4 CTL IFN-g Donor T Cell Target cell apoptosis (III) (II) CD8 CTL Cellular and Donor TNF-a IL-1 inflammatory T-cell Th 1 CD8 CTL effectors activation III a) T-Cell migration

  2. BB&MT 12: 2-8, 2006

  3. Tissue-tropic effector T cells: generation and targeting Opportunities Nature Review Immunology September 2006

  4. (I) Conditioning Tissue Damage Host Small tissues intestine LPS TNF-a IL-1 LPS f M APC TNF-a IL-1 CD4 CTL IFN-g Donor T Cell Target cell apoptosis (III) (II) CD8 CTL Cellular and Donor TNF-a IL-1 inflammatory T-cell Th 1 CD8 CTL effectors activation III b) Tissue Damage

  5. Inflammatory bowel diseases:Mucosa associated receptors (PRM) decide on tolerance versus activation

  6. NOD2/CARD15 variants associate with severe GvHD

  7. Mesenchymal Stem Cells And GvHD?

  8. Chronic Graft-versus-Host Disease

  9. Gilliam and Murphy, GVHD 2nd ed., 1997, p. 299 Chronic Acute Endothelial Phase Lichenoid Phase Epidermotropic and Target Cell Phase Sclerodermatous Phase

  10. 1) Haploidentical P  F1 (MHC I, II, minor H)  B6  B6D2F1: acute GVHD  D2  B6D2F1: chronic GVHD  D2:  CD8+,  IFNg More CD8s convert to acute GVHD 2) B10.D2  Balb (minor H) Skin disease, immunodeficiency  Sub-lethal radiation (600 day) Lethal radiation  acute GVHD (mixed chimerism needed for chronic?) Hakim and Mackail, GVHD 2nd ed

  11. BB & MT 8:656-661 (2002) Blood. 2005;106:3308-3313 Is T-cell depletion associated with less chronic GVHD ?

  12. Amplified clonal T-cell & c.GvHD. BMT 2002; 30: 509-15 • OX40 (CD134) CD4+ CD8+ T-cell & c.GvHD. Blood 2001; 98: 3162-64 both OX40+ CD4+ and OX40+ CD8+ T cells were higher in patients with c.GVHD than those without ( P< .0001 and P< .001, respectively)

  13. High levels of IL-1, IL-6, IFN, and TNF are associated with more severe chronic GVHD • High serum TGF also was associated with chronic GVHD independent of platelet and white blood cell counts • Patients with chronic GVHD have low levels of IL-10 ( anti-inflammatory) and Ig production Review in BB&MT 9:215–233 (2003)

  14. Blood. 2005;105:2973-2978 DBY; UTY; ZFY; RPS4Y; EIF1AY Transplantation. 1988;46:238–240. Experimental Hematology 34 (2006) 389–396

  15. 1985-2000: • 198 patients / HLA id. sibling D • Good risk ; i.e. AML CR, CML 1st CP, SAA • > 1year without relapse

  16. 1985-2000:

  17. 2nd ESH EBMT Teaching course GvHD / GvL 2007 N. Engl. J. Med. 353;13: September 29, 2005

More Related