• 胸腺

1. Cortex:
   a) Immature thymocytes
   b) Macrophages
   c) Cortical epithelium
2. Medulla:
   a) Mature thymocytes
   b) Macrophages
   c) B cells
   d) Medullary epithelium

• 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.

• 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.

• LMP就离开骨髓去了胸腺了

• Notch signaling:

1. Commitment to the T-cell lineage rather than B-cell lineage occurs in the thymus following Notch signaling.
2. 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.

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T细胞发育阶段图

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T细胞发育阶段：

1. 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
2. Double positive:
   a) α链重排
   b) 表达TCR-CD3复合体，ready for selection
   c) postive selection
3. Single positive

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• The first cell-surface molecules specific for T cells: CD2 and Thy-1(mice)

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• 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:

1. induce DN4: cell proliferation
2. the arrest of futher β-chain gene rearrangement：磷酸化并降解RAG-2
3. the expression of both CD8 and CD4.

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• double positive --positive selection -- single positive -- negative selection

• 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。

• 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.

• 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.

• A single functional β chain can be assiciated with many different α chains in the progeny cells.

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TCR重排

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α链重排

• 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。

• 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.

• 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.