G. S / AIH 2006 Graft-versus-Host disease Physiopathology III a) T-Cell migration.

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Presentation transcript:

G. S / AIH 2006 Graft-versus-Host disease Physiopathology III a) T-Cell migration

G. S / AIH 2006 Graft-versus-Host disease Physiopathology BB&MT 12: 2-8, 2006

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Tissue-tropic effector T cells: generation and targeting Opportunities Nature Review Immunology September 2006

G. S / AIH 2006 Graft-versus-Host disease Physiopathology III b) Tissue Damage

G. S / AIH 2006 Graft-versus-Host disease Physiopathology

G. S / AIH 2006 Graft-versus-Host disease Physiopathology

G. S / AIH 2006 Graft-versus-Host disease Physiopathology

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Inflammatory bowel diseases: Mucosa associated receptors (PRM) decide on tolerance versus activation

G. S / AIH 2006 Graft-versus-Host disease Physiopathology NOD2/CARD15 variants associate with severe GvHD

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Mesenchymal Stem Cells And GvHD?

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Chronic Graft-versus-Host Disease

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Acute Endothelial Phase Epidermotropic and Target Cell Phase Lichenoid Phase Sclerodermatous Phase Chronic Gilliam and Murphy, GVHD 2nd ed., 1997, p. 299

G. S / AIH 2006 Graft-versus-Host disease Physiopathology 1) Haploidentical P  F1 (MHC I, II, minor H)  B6  B6D2F1: acute GVHD  D2  B6D2F1: chronic GVHD  D2:  CD8+,  IFN  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

G. S / AIH 2006 Graft-versus-Host disease Physiopathology

G. S / AIH 2006 Graft-versus-Host disease Physiopathology

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Is T-cell depletion associated with less chronic GVHD ? BB & MT 8: (2002) Blood. 2005;106:

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Amplified clonal T-cell & c.GvHD. BMT 2002; 30: OX40 (CD134) CD4+ CD8+ T-cell & c.GvHD. Blood 2001; 98: both OX40+ CD4+ and OX40+ CD8+ T cells were higher in patients with c.GVHD than those without ( P<.0001 and P<.001, respectively)

G. S / AIH 2006 Graft-versus-Host disease Physiopathology 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)

G. S / AIH 2006 Graft-versus-Host disease Physiopathology Transplantation. 1988;46:238–240. Experimental Hematology 34 (2006) 389–396 DBY; UTY; ZFY; RPS4Y; EIF1AY Blood. 2005;105:

G. S / AIH 2006 Graft-versus-Host disease Physiopathology

G. S / AIH 2006 Graft-versus-Host disease Physiopathology

G. S / AIH 2006 Graft-versus-Host disease Physiopathology : 198 patients / HLA id. sibling D Good risk ; i.e. AML CR, CML 1st CP, SAA > 1year without relapse Prognostic factoraHR (95%CI)*P Extensive chronic GvHD within 1 yr 2.94 ( )0.013 TBI or TAI3.11 ( )0.016 Negative CMV donor to positive recipient 2.53 ( )0.033

G. S / AIH 2006 Graft-versus-Host disease Physiopathology :

G. S / AIH 2006 Graft-versus-Host disease Physiopathology N. Engl. J. Med. 353;13: September 29, nd ESH EBMT Teaching course GvHD / GvL 2007