Limited role of CD28-mediated signals in T helper subset differentiation.
Limited role of CD28-mediated signals in T helper subset differentiation.
复制标题
DOI：
10.1084/jem.184.3.803
复制
发表时间：
1996-09-01
期刊：
影响因子：
--
通讯作者：
Reiner SL
中科院分区：
文献类型：
--
作者：
Brown DR;Green JM;Moskowitz NH;Davis M;Thompson CB;Reiner SL
cd28介导的信号在T辅助细胞成熟中的作用尚不完全清楚。我们测试了在CD4+、T细胞分化的几种系统中，通过CD28对共刺激的需求。体内启动CD28基因破坏小鼠（CD28-/-）产生正常水平的抗原特异性干扰素γ，但在体外再刺激后显著降低白细胞介素4 （IL-4）水平。C57BL6 CD28-/-小鼠对利什曼病病原微生物的反应完全能够控制感染，并表现出正常的T辅助1应答。BALB/c CD28-/-小鼠出乎意料地表现出对L. major的正常易感性。BALB/c CD28-/-小鼠在引流淋巴结中出现高水平的IL-4 mRNA和蛋白诱导。此外，体内中和IL-4可逆转BALB/c CD28-/-小鼠的易感性。在体外CTLA4Ig的作用下，我们还激活了BALB和C57BL背景的携带cd28的转基因T细胞。在没有共刺激的情况下，BALB细胞比C57BL细胞产生IL-4的能力更强。包括共刺激信号、遗传多态性和免疫原性质在内的多种因素都影响T辅助表型承诺，但这些结果提供了证据，证明CD28不是产生Th1或Th2应答的绝对必要条件。
The role of CD28-mediated signals in T helper cell maturation is not fully understood. We tested the requirement for costimulation through CD28 in several systems of CD4+, T cell differentiation. In vivo priming of mice with genetic disruption of CD28 (CD28-/-) yielded normal levels of antigen-specific interferon gamma production but markedly diminished levels of interleukin 4 (IL-4) after in vitro restimulation. In response to the pathogenic microbe, Leishman a major, C57BL6 CD28-/- mice were fully capable of controlling infection and exhibited a normal T helper 1 response. BALB/c CD28-/- mice unexpectedly exhibited normal susceptibility to L. major. BALB/c CD28-/- mice developed high levels of IL-4 mRNA and protein induction in the draining lymph nodes. In addition, susceptibility of BALB/c CD28-/- mice was reversed by neutralization of IL-4 in vivo. We also activated transgenic CD28-bearing T cells from the BALB and C57BL background in vitro in the presence of CTLA4Ig. BALB cells had greater IL-4 producing capacity than C57BL cells in the absence of costimulation. Diverse factors including costimulatory signals, genetic polymorphism, and the nature of the immunogen all influence T helper phenotype commitment, but these results provide evidence that CD28 is not an absolute requirement for generating either Th1 or Th2 responses.
登录
查看更多内容
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
影响因子：
56.9
作者：
Guler, ML;Gorham, JD;Murphy, KM
通讯作者：
Murphy, KM
影响因子：
64.5
作者：
KUCHROO, VK;DAS, MP;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
影响因子：
5.4
作者：
KING, CL;STUPI, RJ;THYPHRONITIS, G
通讯作者：
THYPHRONITIS, G
影响因子：
32.4
作者：
GREEN, JM;NOEL, PJ;THOMPSON, CB
通讯作者：
THOMPSON, CB