Allo-HSCT: Understanding GVHD and Immune Microenvironment

1. Allo-Hematopoietic Stem Cell Transplantation 卓越2班5组

2. 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. • Theory of Cytokine Storm • Functions of cells in GVHD T cells NK cells • Hematopoietic microenvironment(造血微环境) • Progress of Allo-HSCT

3. 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

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

6. Activation and proliferation of donor T lymohocyte

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

8. 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.

9. 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)

10. 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

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

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

13. Negative effects • If the microenvironment is abnormal, it cannot provide signals for HSC self-renew and differentiation, which leads to the afunction of CD34+ cells. • It protect HSC LSC at the same time, which contributes to the immunological escape of leukaemic cells.

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

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