Effects of vaccine adjuvant on hematopoiesis

• Main Authors: Kai-Wen Cheng, 鄭凱文
• Other Authors: 楊雅雯
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/10709867797914752289

碩士 === 國立臺灣大學 === 藥學研究所 === 104 === The objective of this study was to examine the immunological effect induced by the L121-adjvant (L121-adj.), an emulsion vaccine adjuvant consisting of Pluronic L121, Tween 80, and squalane, including the cytotoxicity T lymphocyte (CTL) response and the differentiation of B cells, T cells, and the hematopoietic stem/progenitor cells (HSPCs). Vaccination of B16F10 melanoma-bearing mice with L121-adj. containing ovalbumin (OVA) induced an antigen-specific CTL response, resulted in an inhibition of tumor growth with an increased the survival rate. Flow cytometric analysis illustrated both dendritic cells and granulocytes were recruited to the injection sites after vaccination, and antigens were transported to draining lymph nodes by the antigen presenting cells (APCs). Accelerated production of granulocytes was observed in the bone marrow, in response to inflammation induced by vaccination, followed by moving into the spleen. Dendritic cells were able to effectively cross-present antigen in vivo via MHC-I molecule and activate the CD8+ T cells. Depletion of granulocytes prior to immunization resulted in an enhanced CTL response. Injection of L121-adj. promoted the translocation of B cell precursors from bone marrow to the spleen, resulted in the differentiation of transitional B cells into marginal zone B cells and follicular B cells, followed by the formation of germinal center and plasma B cells. Positive selection of developing T cells in the thymus was accelerated by the treatment of L121-adj., resulted in a significant production of mature CD4+ T cells. Modification of hematopoietic homeostasis was also noticed after vaccination of animals with L121-adj. Flow cytometric analysis showed marked increase of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem cells (HSCs) and consequently the granulocyte-macrophage progenitors (GMPs), presumably at an expense of the common myeloid progenitors (CMPs). Generation of F4/80+ and Ly6G+ cells from LSK, CMPs, and GMPs was profoundly increased due to the presence of granulocyte colony-stimulating factor (G-CSF) in the serum of immunized mice. Taken together, injection of mice with L121-adj. exhibited several immunological effects, including the recruitment of dendric cells for the activation of CTL, promoting the differentiation and maturation of progenitors of B and T progenitors into functional lymphocytes. L121-adj. also triggers the differentiation and proliferation of hematopoietic stem/progenitor cells (HSPCs), giving rise to the generation of granulocytes in the bone marrow of immunized animals.