CD28 promotes CD4+ T cell clonal expansion during infection independently of its YMNM and PYAP motifs.
CD28 promotes CD4+ T cell clonal expansion during infection independently of its YMNM and PYAP motifs.
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DOI：
10.4049/jimmunol.1103231
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发表时间：
2012-09-15
期刊：
影响因子：
--
通讯作者：
Jenkins MK
中科院分区：
文献类型：
--
作者：
Pagán AJ;Pepper M;Chu HH;Green JM;Jenkins MK
CD28是通过其TCR刺激的CD4+ T细胞的最大增殖所需的。CD28胞质尾区的两个位点，即募集PI3 K并激活NFκB的YMNM序列和募集Lck的PYAP序列，是负责这些生物学效应的信号转导子的候选者。我们通过跟踪多克隆肽：MHCII特异性CD4+ T细胞在这些位点突变的小鼠体内来测试这一命题。缺乏CD28或其胞质尾的小鼠具有与野生型小鼠相同数量的对肽：MHCII配体特异性的初始T细胞。然而，在感染表达抗原肽的细菌后，突变细胞产生的效应细胞和记忆细胞是野生型T细胞的十分之一。值得注意的是，具有突变的PI3K结合位点、突变的PYAP位点或两种突变的T细胞增殖到与野生型T细胞相同的程度。唯一观察到的缺陷是，具有突变的PYAP或Y170F位点的T细胞在没有佐剂的情况下对肽的应答比野生型T细胞更弱地增殖。这些结果表明，在细菌感染期间，CD28通过从胞质尾中未发现的位点发出的信号增强T细胞增殖。
CD28 is required for maximal proliferation of CD4+ T cells stimulated through their TCRs. Two sites within the cytoplasmic tail of CD28, a YMNM sequence that recruits PI3K and activates NFκB, and a PYAP sequence that recruits Lck, are candidates as transducers of the signals responsible for these biological effects. We tested this proposition by tracking polyclonal peptide:MHCII-specific CD4+ T cells in vivo in mice with mutations in these sites. Mice lacking CD28 or its cytoplasmic tail had the same number of naive T cells specific for a peptide:MHCII ligand as wild-type mice. However, the mutant cells produced one-tenth as many effector and memory cells as wild-type T cells following infection with bacteria expressing the antigenic peptide. Remarkably, T cells with a mutated PI3K binding site, a mutated PYAP site, or both mutations proliferated to the same extent as wild-type T cells. The only observed defect was that T cells with a mutated PYAP or Y170F site proliferated even more weakly in response to peptide without adjuvant than wild-type T cells. These results show that CD28 enhances T cell proliferation during bacterial infection by signals emanating from undiscovered sites in the cytoplasmic tail.
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DOI：
10.1084/jem.20052230
发表时间：
2006-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Friend LD;Shah DD;Deppong C;Lin J;Bricker TL;Juehne TI;Rose CM;Green JM
通讯作者：
Green JM
DOI：
10.1084/jem.190.3.375
发表时间：
1999-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Holdorf AD;Green JM;Levin SD;Denny MF;Straus DB;Link V;Changelian PS;Allen PM;Shaw AS
通讯作者：
Shaw AS
影响因子：
4.4
作者：
Bonnevier, JL;Mueller, DL
通讯作者：
Mueller, DL
影响因子：
4.4
作者：
Burr, JS;Savage, NDL;Green, JM
通讯作者：
Green, JM
影响因子：
3.3
作者：
Edinger, AL;Thompson, CB
通讯作者：
Thompson, CB