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CD30最早被確認成診斷哈杰金氏淋巴瘤(Hondgkins lymphoma)
的腫瘤標記。目前己知，除了在哈杰金氏症(Hondgkins disease
)的黎特氏細胞(Reed-Sternberg cells)外，它也能表現在各種不同細胞上，
包括活化的Ｔ細胞，巨噬細胞，和其他非哈杰金氏症的血液腫瘤細胞。CD30L
是與CD30受體互為配受體系統之配體蛋白。這一對配受體系統隸屬於TNF/NGF
(tumor necrosis factor; nerve growth factor) 與TNFR/NGFR (tumor necro
factor receptor; nerve growth factor receptor)超級家族成員之一
，這些眾多成員以其特有的生物活性在生物體內組成一個複雜的網路系統，
媒藉著不同類型細胞的增殖，活化，分化，死亡等歧異功能。經由
CD30-CD30L交互作用傳遞的訊息也因細胞種類之不同，有死亡與生長
分化極端相異之細胞多效性之特色 (pleiotropic effect)。根據CD30基
因剃除老鼠的實驗結果顯示，會有較多數目的胸腺細胞 (thymocytes)，
在進一步的研究發現CD30是參與在胸腺內Ｔ細胞負性篩選作用的協同受體分子。
然而關於CD30L的分佈及與CD30受體的相關性研究所知卻極有限。
本論文實驗主旨在找尋CD30與CD30L分子同時參與在胸腺負性篩選機制
的直接証據。選用正常品系小鼠當實驗模型，經由RT-PCR結果顯示胸
腺內CD30 mRNA明顯表現在出生第零到第七天 (P0∼P7 stage) 新生幼鼠階
段；CD30L mRNA則明顯表現在出生兩週到八週階段 (2W∼8W)；隨著不同出生
年齡它們互呈一個消長變化趨勢。經由免疫組織染色分析不同階段小鼠胸腺
發現：CD30受體分子少量分佈在幼鼠 (P7 stage) 胸腺髓質部的古型細胞上
；CD30L配體分子則廣佈在成鼠 (６週大) 大多數胸腺細胞上。結合著流式
細胞儀分杵，証明表現CD30L蛋白的細胞是胸腺內未成熟的Ｔ細胞，進一? B比較出生3天與3週大階段胸腺檢體，發現CD30+ cells只佔極少比例
(1∼3%)，而CD30L+ cells則有明顯增多趨勢 (從2%增至60%)。收集人類
四個月大流產胎兒胸腺檢體分析，同樣印証CD30受體只分佈在極少之胸腺
髓質部大型細胞上，而這個階段中偵測不到CD30L的存在。本論文以正常
小鼠當實驗模型發現CD30受體與CD30L配體在表現量頂峰期及組織分佈位
置的不一致性，且表現在多數胸腺細胞(thymocytes) 上的是配體而非受
體分子，暗示著這對配受體分子也許不是直接負責胸腺負性篩選作用。
在除了相關文獻以CD30缺乏小鼠所作的實驗外，我的實驗結果提供了一
些新的証據給未來實驗方向，進一步釐清CD30-CD30L這對配受體參與在胸腺
Ｔ細胞發育上的角色。
CD30 is first identified as a tumor marker for neoplastic cells
of Hodgkins (HD) lymphoma. It is now known that CD30 can be expressed
by a variety of cells, including activated T cells, macrophages, and
other non-HD lymphoma cells. Its cognate ligand protein, CD30L, has
also been identified. CD30L and CD30 belong to the TNF/NGF cytokine
and TNFR/NGFR superfamily, respectively. Most members of this superfamily
are known to work as a complex network in regulating cell proliferation,
differentiation, survival or death. For example, interaction of CD30 and
CD30L has pleiotrophic activity in mediating cell death, proliferation
and differentiation. The study of CD30-deficient mice demonstrated an
increased numbers of thymocytes. Further in vitro and in vivo studies
revealed that CD30 is involved in the signaling of thymic negative
selection in mouse thymus. Very little is known about the distribution
of CD30 ligand and its correlation with receptor.The purpose of this
study is to investigate the interaction of CD30 receptor and ligand
in thymic negative selection. Using RT-PCR analysis, CD30 transcripts
can be detected in mouse thymus up-to the 7th day of postnatal life,
while the significant expression of CD30 ligand in thymus appeared only
after two weeks. Flow cytometry study with 3-day- and 3-week-old mice,
further confirmed an unparalleled expression of CD30 ligand and its
receptor in pup thymus. Immunohistochemical staining was used to identify
the cell types and localization for CD30 and CD30 ligand expression.
In 7-day-old mouse, CD30 receptor is expressed in a small numbers of
large cells that mainly located in the thymic medulla while little numbers
signal of CD30 ligand was found at this stage of thymic cortex. However,
CD30 ligand can be detected in most cortical thymocytes of 6-week-old
mouse. The study of human embryos collected from miscarriages at
20∼24-week-gestation also supports the finding in mouse, that the
expression of CD30 ligands was undetectable at this early stage and
very few of CD30 receptors were expressed in the large cells within
thymic medulla. My data demonstrated a temporal and unparalleled expression
between CD30 receptor and its ligand, and a lack of expression of CD30
(as a receptor) in most thymocytes, indicating that CD30 ligand might
not be directly responsible for negative selection in thymus. Further
study is required to clarify the mechanism involved in CD30 signalings
pathway in thymic T cell development.
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