AlloHematopoietic Stem Cell Transplantation 2 5 l AlloHematopoietic

Allo-Hematopoietic Stem Cell Transplantation 卓越2班 5组

l Allo-Hematopoietic Stem Cell Transplantation ----Allo-HSCT Graft-versus-Host Disease(GVHD) GVHD: a disease occuring in bone marrow transplant recipients that is caused by the reaction of mature T cells in the marrow graft with alloantigens on host cells. The diease most often affects the skin, liver, and intestines. l Theory of Cytokine Storm l Functions of cells in GVHD T cells NK cells l Hematopoietic microenvironment(造血微环境) l Progress of Allo-HSCT

Theory of Cytokine Storm �Damage of tissue in pretreatment host's MHC protein↑ → donor's immunocytes recognize host cells↑ �Activation and proliferation of donor's T lymphocytes �Cells and inflammatory factors attack target tissue leading to GVHD

Tissue damage �The spread of cytokin caused by pretreatment or inflammation. Donor immune cells have better distinguishment on receptor MHC.

Activation and proliferation of donor T lymohocyte

Cell and inflammatory factor attack target cell �monocyte/neutrophil secret inflammatory factor＋CTL →damage totarget tissue and apoptosis.

NK cells �KIR- Killer immunoglobin-like receptor �KIR bind with MHC-I �KIR mismatching: The recipient cell lacks “correct” MHC-I molecules, fails to offer inhibiting signal to donor KIR.

Immune Environment of Allo-HSCT �Hematopoietic microenvironment consists of a group of histocytes and matrix. And it can preserve and regulate the local tissue microenvironment of HSC through cell-cell contact and signal molecules. And its functional unit called niche(龛)

Bone marrow �Bone marrow is the first and second class immune organ. It has many kinds of immune cells including T lymphocyte, B lymphocyte, NK and DC. These cells and the cytokin they secret and the signaling pathway the mediate form the immune niche

Effects of Immune Microenvironment Positive effects �Immune cells provide immunological barrier for regulation of HSC homeostasis and HSC proliferation and differentiation.

Positive effects �Promote the homing of stem cells, have great influance on the differentiation from CMP （髓系共同祖细胞) to MEP（巨核／红系祖细胞).

Negative effects �If the microenvironment is abnormal, it cannot provide signals for HSC self-renew and differentiation, which leads to the afunction of CD 34+ cells. �It protect HSC LSC at the same time, which contributes to the immunological escape of leukaemic cells.

Progress of Allo-HSCT Transplantation �Use of immunosuppressant: MTX（甲氨蝶呤), Cs. A（环孢素) etc. �Mesenchymal stem cell transplantation at early stage. �Build chimaera to induce immune tolerance.