臺灣博碩士論文加值系統

胸腺是T淋巴球發育成熟的重要器官，由骨髓而來的stem cells，經 過了
TCR gene rearrangement，positive及negative selection,產生出
single positive CD4或CD8 T cells，具有self-MHC restricted及self-
antigen tolerant的T cell receptor repertoire。接著，它們會移出胸
腺，循環至週邊行其免疫功能.本篇論文所研究的是剛在胸腺發育成熟的
CD4 T cells與已循環至週 邊的CD4 T cells，它們在cytokine(IL-2、
IL-4及 IFN)production上的特性。在CD4+ T cells中，有一群TCR
repertoire非常小，且非傳統MHC Class II restricted，而是MHC Class
I(CD1) restricted的NK1.1+CD4+ T cells，近年來的報告指出，它們透
過in vitro primary stimulation或是in vivo TCR crosslinking，在短
時間(1-2小時)之內，即有大量的IL-4的 production，它們提供了大量的
IL-4，被認為扮演著重要的免疫調 控角色。根據我們的研究結果，在去
除了這一群NK1.1+CD4+ T cells 之後，剛在胸腺發育成熟的傳統型CD4+
T cells，透過primary stimulation ，仍有IL-4及IFN production，但
此能力會隨著移出胸腺的時間而漸漸消失，相對地IL-2 production的能
力則上升，最後變成IL-2-only的producer。由於每天均有這些一般、傳
統型的CD4+ T cells，在胸腺被大量製造出來，這些CD4+NK1.1- T cells
也可能是IL-4及IFN的供應者。在免疫反應中，能在較早期分泌IL-4對於
啟動Th2 type immune response是非常重要的。這一群recent thymic
emigrants在對抗外來抗原或是自體抗原時，有決定Th1或 Th2免疫反應的
潛力。

The thymus plays an important role in the development of
T lymphocytes which undergo T cell receptor rearrangement,
followed by positive and negative selection, resulting in
the shaping of the mature self-MHC restricted and self-
antigen tolerant T cell receptor repertoire. Mature CD4+8-
or CD4-8+ T cells then migrate to and develop further in
peripheral tissues to a stage of functional competence as
effector T cells. In this report, we characterized the
cytokine (IL-2, IL-4 and IFNg) production potential by
conventional CD4+ T cells that have just completed
maturation in the thymus and those that have migrated to
the periphery. NK1.1+CD4+ T cells belong to a subset of
CD4+ T cells characterized by a narrow TCR repertoire
usage, in marked contrast to a very diversified TCR
repertoire among conventional CD4+ T cells. In addition,
NK1.1+CD4+ T cells are MHC class I (CD1)- restricted
rather than MHC class II-restricted. Furthermore, they
are able to produce large quantities of IL-4 upon primary
stimulation in vitro and within minutes upon TCR-
crosslinking in vivo, and have therefore been suggested
to provide an excellent source of IL-4 and play an
important role in immunoregulation. In our studies, after
removal of NK1.1+CD4+ T cells, mature thymus CD4+NK1.1- T
cells were still able to produce good levels of IL-4 and
IFNg but low level of IL-2 upon primary stimulation.
Na鴳e CD4+NK1.1- T cells found in the spleen, on the other
hand, produce high amounts of IL-2, but very little IL-4
and IFNg, indicating that the likely and rapid transition
from IL-4+IFNg+IL-2low to IL-4lowIFNglowIL-2hi producing state
upon emigration of thymic T cells into the periphery.
Because NK1.1-CD4+ T cells constitute the vast majority of
all CD4+ T cells and that they emigrate to peripheral
lymphoid tissues on a continuous basis, these mainstream
conventional CD4+ T cells may also be a ever present
source of IL-4 and IFNg, despite the relative short
duration associated with their IL-4 and IFNg producing
potential. Since early secretion of IL-4 is critical for
the initiation of Th2 type immune response, these
conventional recent emigrants may play a role in
determining and/or regulation of Th1/Th2 immune response
development.