p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement.
p53 prevents maturation to the CD4+CD8+ stage of thymocyte differentiation in the absence of T cell receptor rearrangement.
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在没有T细胞受体重排的情况下，p53防止了胸腺细胞分化的CD4+ CD8+阶段的成熟。
DOI：
10.1084/jem.183.4.1923
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发表时间：
1996-04-01
影响因子：
15.3
通讯作者：
ZunigaPflucker, JC
中科院分区：
文献类型：
--
作者：
Di, JA;Lenardo, MJ;ZunigaPflucker, JC
免疫球蛋白（IG）和T细胞受体（TCR）基因座的重排允许产生具有抗原特异性受体的B和T淋巴细胞。TCR-β链的完全重排和表达使得未成熟的胸腺细胞能够从CD 4-CD 8-分化为重排受损的CD 4 + CD 8+阶段小鼠，例如严重联合免疫缺陷（SCID）小鼠或重组酶激活基因缺陷（RAG-/-）小鼠，缺乏成熟的B和T淋巴细胞。来自这些小鼠的胸腺细胞在T细胞发育的CD 4-CD 8-阶段被阻滞。我们先前观察到暴露于γ辐射的RAG-2-/-小鼠的胸腺细胞从CD 4-CD 8-分化为CD 4 + CD 8+，而没有TCR-β链重排。我们现在报告，辐射RAG-2-/-胸腺细胞在p53基因位点发生直接体细胞突变，并且p53失活与RAG-2-/-胸腺细胞成熟到CD 4 + CD 8+阶段有关。RAG 2-/-和p53-/-双缺陷小鼠的产生揭示，在不存在TCR-β链重排的情况下，p53功能的丧失足以使CD 4-CD 8-胸腺细胞分化成T细胞发育的CD 4 + CD 8+阶段。我们的数据提供了一种新的p53介导的检查点在胸腺细胞发育的早期，调节CD 4-CD 8-转化为CD 4 + CD 8+胸腺细胞的证据。
Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen- specific receptors. Complete rearrangement and expression of the TCR- beta chain enables immature thymocytes to differentiate from the CD4- CD8- to the CD4+CD8+ stage mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG-/-) mice, lack mature B and T lymphocytes. Thymocytes from these mice are arrested at the CD4-CD8- stage of T cell development. We previously observed that thymocytes from RAG-2-/- mice exposed to gamma radiation differentiate from CD4- CD8- into CD4+CD8+ without TCR-beta chain rearrangement. We now report that irradiated RAG-2-/- thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RAG2-/- thymocytes to the CD4+CD8+ stage. Generation of RAG2-/- and p53-/- double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4-CD8- thymocytes to differentiate into the CD4+CD8+ stage of T cell development. Our data provide evidence for a novel p53 mediated checkpoint in early thymocyte development that regulates the transition of CD4-CD8- into CD4+CD8+ thymocytes.
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影响因子：
64.8
作者：
MOMBAERTS, P;CLARKE, AR;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
32.4
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
影响因子：
56.9
作者：
SHINKAI, Y;KOYASU, S;ALT, FW
通讯作者：
ALT, FW
DOI：
10.1073/pnas.90.12.5742
发表时间：
1993-06-15
影响因子：
11.1
作者：
LEE, JM;BERNSTEIN, A
通讯作者：
BERNSTEIN, A
影响因子：
32.4
作者：
MOMBAERTS, P;ANDERSON, SJ;TONEGAWA, S
通讯作者：
TONEGAWA, S