Characterization of the early stages of thymic NKT cell development.
Characterization of the early stages of thymic NKT cell development.
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DOI：
10.1084/jem.20050456
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发表时间：
2005-08-15
期刊：
影响因子：
--
通讯作者：
Bendelac A
中科院分区：
文献类型：
--
作者：
Benlagha K;Wei DG;Veiga J;Teyton L;Bendelac A
达到成熟的热稳定抗原（HSA）低胸腺发育阶段后，CD1D限制的Vα14-Jα18胸腺细胞经历了膨胀和差异性步骤的特征序列，从而导致外周素毒素-4/Interferon-gresson-gresson-gresson-γ-生产NKT型NKT。但是，它们更不成熟的Hsahigh前体仍然难以捉摸，很难明确地确定NKT细胞是否起源于A CD4+ CD8+双阳性（DP）阶段，当CD4+和CD4-CD8-双重（DN）NKT子集形成时，我们使用了基于CD1D Tetramer的富集策略新生小鼠，包括弹性dplow阶段和CD4+阶段，这些频率约为10-6。非个人化，并且已经表现出相同的Vβ8偏置，表征了成熟的NKT细胞。细胞，DN NKT细胞并非源自PTα的途径，绕过DP阶段，而是在短时间的时间窗口中产生从HSALOW NK1.1NEG CD4细胞的一部分的转化中。
Upon reaching the mature heat stable antigen (HSA)low thymic developmental stage, CD1d-restricted Vα14-Jα18 thymocytes undergo a well-characterized sequence of expansion and differentiation steps that lead to the peripheral interleukin-4/interferon-γ–producing NKT phenotype. However, their more immature HSAhigh precursors have remained elusive, and it has been difficult to determine unambiguously whether NKT cells originate from a CD4+CD8+ double-positive (DP) stage, and when the CD4+ and CD4−CD8− double-negative (DN) NKT subsets are formed. Here, we have used a CD1d tetramer-based enrichment strategy to physically identify HSAhigh precursors in thymuses of newborn mice, including an elusive DPlow stage and a CD4+ stage, which were present at a frequency of ∼10−6. These HSAhigh DP and CD4+ stages appeared to be nondividing, and already exhibited the same Vβ8 bias that characterizes mature NKT cells. This implied that the massive expansion of NKT cells is separated temporally from positive selection, but faithfully amplifies the selected TCR repertoire. Furthermore, we found that, unlike the DN γδ T cells, the DN NKT cells did not originate from a pTα-independent pathway bypassing the DP stage, but instead were produced during a short window of time from the conversion of a fraction of HSAlow NK1.1neg CD4 cells. These findings identify the HSAhigh CD4+ stage as a potential branchpoint between NKT and conventional T lineages and between the CD4 and DN NKT sublineages.
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主要组织相容性复合体 I 类相关分子控制小鼠肝脏中自然杀伤 1.1+ T 细胞受体-α/β+ 细胞的 CD4+8- 和 CD4-8- 亚群的发育。
影响因子：
15.3
作者：
Ohteki, Toshiaki;Macdonald, H. Robson
通讯作者：
Macdonald, H. Robson
影响因子：
64.8
作者：
Mattner, J;DeBord, KL;Bendelac, A
通讯作者：
Bendelac, A
影响因子：
15.3
作者：
Benlagha, K;Weiss, A;Beavis, A;Teyton, L;Bendelac, A
通讯作者：
Bendelac, A
DOI：
10.1073/pnas.93.13.6516
发表时间：
1996-06-25
影响因子：
11.1
作者：
Makino, Y;Kanno, R;Taniguchi, M
通讯作者：
Taniguchi, M
DOI：
10.1084/jem.175.3.731
发表时间：
1992-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bendelac A;Matzinger P;Seder RA;Paul WE;Schwartz RH
通讯作者：
Schwartz RH