- 胸腺
- Cortex:
a) Immature thymocytes
b) Macrophages
c) Cortical epithelium - Medulla:
a) Mature thymocytes
b) Macrophages
c) B cells
d) Medullary epithelium
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In mice, the thymus continues to develop for 3-4 weeks after birth, whereas in humans it is fully developed at birth. The rate of T cell production by thymus is greatest before puberty. After puberty. the thymus begins to shrink, and the production of new T cells in adults is reduced, although it dose continue throughout life.
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青春期之后,进行胸腺切除也不会影响T细胞的数量或者功能。---Once the T cell repertoire is established, immunity can be sustained without the production of significant numbers of new T cells. The pool of peripheral T cells is instead maintained by long-lived T cells and also by division of some mature T cells.
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LMP就离开骨髓去了胸腺了
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Notch signaling:
- Commitment to the T-cell lineage rather than B-cell lineage occurs in the thymus following Notch signaling.
- Notch signaling is required throughout T-cell development and is also throught to help regulate other T-cell lineage choices, including the α:β versus γ:δ.
3.Notch---induce 2 TF: TCF-1 & GATA3---initiate T-lineage-specific-genes: CD3-related genes, Rag1...
- TCF-1和GATA-3 are not sufficient to induce the entire program of T-cell-specific gene expression. 还需要第三种重要的转录因子——Bcl11b: is required to induce T-lineage commitment by restrictiing progenitor cells from adopting alternative fates.
T细胞发育阶段图
T细胞发育阶段:
- Double negative
a) DN1: CD44+CD25-
b) DN2: CD44+CD25+,开始β链重排(D-J)
c) DN3: CD44lowCD25-,β链重排(V-DJ), β链与pTα链形成preTCR
d) DN4 : CD44-CD25-,preTCR诱导T细胞开始增殖 - Double positive:
a) α链重排
b) 表达TCR-CD3复合体,ready for selection
c) postive selection - Single positive
- The first cell-surface molecules specific for T cells: CD2 and Thy-1(mice)
- As with the pre-B-cell receptor, the assembly of the CD3:pre-TCR complex causes constitutive signaling that dose not require interaction with a ligand.--leads to:
- induce DN4: cell proliferation
- the arrest of futher β-chain gene rearrangement:磷酸化并降解RAG-2
- the expression of both CD8 and CD4.
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double positive --positive selection -- single positive -- negative selection
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most T cell development takes place in the cortex; only mature single-positive thymocytes are seen in medulla(但LMP进入胸腺的时候进的是皮质髓质交界处)。阳性选择之后,T细胞进入髓质。
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The γ and δ loci are the first to undergo rearrangement, followed shortly thereafter by the β locus. In addition, the δ locus is contained within the α locus, so rearrangements at the α locus eliminate the δ coding sequences on the chromosome.
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During the proliferation of DN4 cells triggered by expression of the pre-T-cell receptor, the RAG-1 and RAG-2 genes are repressed (see Fig. 8.18). Hence, no rearrangement of the α-chain locus occurs until the proliferative phase ends, at which time RAG-1 and RAG-2 are transcribed again, and the functional RAG-1:RAG-2 complex accumulates.
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A single functional β chain can be assiciated with many different α chains in the progeny cells.
TCR重排
α链重排
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与B细胞不同, α链重排并不会随着一条α链重排结束而停止,其停止条件为识别自身MHC分子提呈的抗原肽,即阳性选择。因此一个T细胞是可能产生两种α链的。
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This phase of gene arrangement lasts for 3 or 4 days in the mouse and ceases only when positive selection occurs as a consequence of receptor engagement, or when the cell dies.
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However, only one of the two receptors is likely to be able to recognize peptide presented by a self MHC molecule, and so the T cell will have only a single functional specificity.
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