IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells.
IL-2 and antigen dose differentially regulate perforin- and FasL-mediated cytolytic activity in antigen specific CD4+ T cells.
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DOI：
10.1016/j.cellimm.2009.03.002
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发表时间：
2009
影响因子：
4.3
通讯作者：
Swain, Susan L.
中科院分区：
文献类型：
--
作者：
Brown, Deborah M.;Kamperschroer, Cris;Dilzer, Allison M.;Roberts, Deborah M.;Swain, Susan L.
然而，CD4T细胞效应器可以通过穿孔素介导的细胞溶解机制促进对致命流感病毒的存活；然而，我们对幼稚的CD4细胞如何分化为II类限制性杀伤细胞的了解仍然不清楚。为了解决这个问题，TCRTGCD4细胞在体外被激活，并检测它们裂解靶细胞的能力。我们发现，细胞因子极化的CD4T细胞效应器显示出Th0>；Th1>；Th2的杀伤活性。此外，IL-4还能抑制细胞毒性CD4细胞的产生。但IL-6、转化生长因子-β、IL-10、IL-12或肿瘤坏死因子-α不是诱导CD_4效应细胞杀伤活性的必要条件。抗原剂量对细胞毒性有显著影响：低浓度的多肽比相对高浓度的多肽诱导更强的细胞杀伤活性。在低浓度时，外源性IL-2对颗粒酶B(GRB)的表达和穿孔素介导的裂解是必需的。因此，低抗原剂量和通过IL-2的早期激活信号将CD4T细胞反应导向具有穿孔素介导的细胞溶解潜力的效应器。这些数据对疫苗的设计具有重要意义，这种疫苗可以在体内诱导细胞溶解的CD4细胞，并提高细胞对病毒和细菌感染的免疫力。
CD4 T cell effectors can promote survival against lethal influenza virus via perforin mediated cytolytic mechanisms, however; our understanding of how naïve CD4 cells differentiate into class II restricted killers remains obscure. To address this, TCR Tg CD4 cells were activated in vitro and examined for their ability to lyse target cells. We found that cytokine polarized CD4 T cell effectors displayed cytolytic activity with the hierarchy Th0>Th1>Th2. Further, IL-4 inhibited the generation of cytotoxic CD4 cells. LPS stimulated B cells and bone marrow derived dendritic cells (BMDC) both induced potent cytolytic activity; however, IL-6, TGF-β, IL-10, IL-12 or TNF-α were not required for inducing cytolytic activity in CD4 effectors. Antigen dose had a marked effect on cytotoxicity: low concentrations of peptide induced more potent cytolytic activity than relatively high concentrations. At low peptide concentration, exogenous IL-2 was necessary to drive granzyme B (GrB) expression and perforin mediated lysis. Thus, low antigen dose and early activation signals via IL-2 direct the CD4 T cell response toward effectors with perforin mediated cytolytic potential. These data have implications for the design of vaccines that may induce cytolytic CD4 cells in vivo and improve cell-mediated immunity to viral and bacterial infections.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
DOI：
10.1084/jem.182.5.1591
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Constant S;Pfeiffer C;Woodard A;Pasqualini T;Bottomly K
通讯作者：
Bottomly K
迁移动力学和1型和2型CD8效应细胞的最终目的地预测防止肺病毒感染的保护。
DOI：
10.1084/jem.189.2.423
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cerwenka A;Morgan TM;Harmsen AG;Dutton RW
通讯作者：
Dutton RW
影响因子：
20.3
作者：
Fujii, S;Shimizu, K;Lotze, MT
通讯作者：
Lotze, MT
影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H