description
Graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT) where immunocompetent donor T cells attack the genetically disparate host cells. GVHD pathophysiology can be summerized in a three-step process. Step 1 involves the development of an inflammatory milieu resulting from damage in the host tissues induced by the preparative chemotherapy or radiotherapy regimen. Damaged tissues secrete inflammatory cytokines, including interleukin 1 (IL-1), and tumor necrosis factor (TNF-alpha ). During step 2, antigen-presenting cells (APCs) trigger the activation of donor-derived T cells, which induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B

external resources
NCBI:83124
KEGG:hsa05332
PUBMED:14556773
PUBMED:17784964
PUBMED:14735553
PUBMED:16412784
PUBMED:17900507
PUBMED:15372473
PUBMED:16147539
PUBMED:12359826
PUBMED:15882431

genes
FAS , FASLG , CD28 , CD80 , CD86 , GZMB , HLA-A , HLA-B , HLA-C , HLA-DMA , HLA-DMB , HLA-DOA , HLA-DOB , HLA-DPA1 , HLA-DPB1 , HLA-DQA1 , HLA-DQA2 , HLA-DQB1 , HLA-DRA , HLA-DRB1 , HLA-DRB5 , HLA-E , HLA-F , HLA-G , IFNG , IL1A , IL1B , IL2 , IL6 , KIR2DL1 , KIR2DL3 , KIR3DL1 , KIR3DL2 , KLRC1 , KLRD1 , PRF1 , TNF ,