許世明2018-07-092018-07-092004http://ntur.lib.ntu.edu.tw//handle/246246/25363人體周邊血液中有二種主要的自然殺手細胞，分別有顯著不同的表面抗原， CD56 + KIR +/- Lectin + 及CD 56 ± KIR + Lectin ± ，本計劃將重細胞發生學的觀點來 澄清這兩種自然殺手細胞的來源。 本計劃至目前為止，已完成下列四項主要目標： 1. 臍帶血CD34 + 幹細胞之分離及擴增 我們已成功將CD34 + 幹細胞由臍帶血分離，在混合白血球介質刺激下，經 培養1~2 個星期後，可以擴增5~10 倍。 2. CD56 表現於約10%的CD34 - 細胞 經過另一組白血球的介質的刺激，我們可以於10%的CD34 - 細胞中發現有 CD56 的表現，這CD56 + 細胞最有可能是NK 母細胞，但是骨髓胜原始細胞 亦不可能排除，我們將進一步分析之。 3. 鼻咽淋巴癌之系源分析 我們用自然殺手細胞類免疫球蛋白之限制性分布，作有診斷及系源認定的標 準，我們發現，大部份鼻咽淋巴癌源自於自然殺手細胞（Am J Path 2001. 159. 1671 ） 4.鼻咽淋巴癌之臨床分析 我們更進一步以白血球表面抗原94 （CD94 ）分析其鼻咽淋巴癌之臨床表現， 發現鼻咽淋巴癌分為CD94 + 及CD94 - 兩種亞型， CD94 + 明顯有較佳預後 （Blood 2003. 102. 2623 ）我們目前正進行比對，以確定這2 種亞型是否就是 分別由CD56 + KIR +/- Lectin + 及CD 56 ± KIR + Lectin ± 這兩種自然殺手細胞演變而 來。There are 2 major subtypes of mature NK-cells with differential surface markers in the peripheral blood, CD56 + KIR +/- Lectin + and CD56 +/- KIR + Lectin +/- . Our proposal is aimed at clarifying the developmental pathway of these 2 subtypes of mature NK-cells. So far, we have achieved the following: I: Isolation and expansion of CD34 + stem cells from umbilical cord blood We have isolated CD34 + stem cells from umbilical cord. We are able to expand the CD34 + Lin- stem cells with the use of an in vitro culture system under cytokine stimulation. An 5-10 fold expansion is achieved after 1-week culture. II: Partial Induction of CD56 expression, suggestive of NK-differentiation The expanded stem cells were further grown for another 1 week, to induce differentiation. Although most cells developed into the myeloid lineage, about 5-10% were CD56 + , suggestive of an NK-lineage. To continue the investigation, we are currently using IL-15 to stimulate proliferation and induction of mature NK-cells. III: Confirmation of lineage assignment of sinonasal lymphoma We have performed an extensive assessment of the lineage assignment of sinonasal lymphomas. We found most sinonasal lymphomas had a restricted killer immunoglobulin-like receptor repertoire, consistent with a NK-lineage. But some cases had a monoclonal T-cell receptor rearrangement plus a restricted killer immunoglobulin-like receptor repertoire, consistent with a mixed NK/T cell lineage. (Am J Path, 2001, 159, 1671.) IV: Clinical correlation and significance. Further analysis of the expression pattern of CD94 (the killer lectin-like receptor) showed that a subset of sinonasal lymphoma had CD94 expression. The CD94 positive subset had a much better prognosis than the CD94-negative subset. (Blood, 2003, 102, 2623) We are currently investigating whether these 2 subsets correspond to the 2 major subsets of mature NK-cells of the peripheral blood.application/pdf76595 bytesapplication/pdfzh-TW國立臺灣大學醫學院免疫學研究所雙系模式細胞介質15(IL15)細胞介質21(IL21)白血球 表面抗原56(CD56)自然殺手細胞類免疫球蛋白(KIR)糖 類接合蛋白(Lectin)白血球球表面抗原94(CD94)dual lineageIL15IL21CD56KIRlectinjournal articlehttp://ntur.lib.ntu.edu.tw/bitstream/246246/25363/1/922314B002118.pdf