A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism.
A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism.
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DOI：
10.1084/jem.187.2.225
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发表时间：
1998-01-19
期刊：
影响因子：
--
通讯作者：
Jenkins MK
中科院分区：
文献类型：
--
作者：
Khoruts A;Mondino A;Pape KA;Reiner SL;Jenkins MK
采用过继转移的方法，研究了脂多糖（LPS）佐剂增强T细胞克隆性扩增的机制。皮下注射可溶性抗原（Ag）导致Ag特异性T细胞在引流淋巴结（LN）中快速和短暂的积累，这之前是白细胞介素（IL）-2的产生。CD 28缺陷型Ag特异性T细胞对可溶性Ag仅产生少量IL-2，并且在LN中的累积程度与野生型T细胞不同。注射Ag和LPS（一种天然免疫佐剂）可增强野生型Ag特异性T细胞的IL-2产生和LN积累，但对CD 28缺陷型Ag特异性T细胞无显著影响。因此，CD 28对于Ag驱动的IL-2产生和体内T细胞增殖至关重要，并且对于LPS介导的这些事件的增强是必不可少的。然而，IL-2产生的增强不能解释T细胞积累的LPS依赖性增加，因为IL-2缺陷的Ag特异性T细胞在LN中比野生型T细胞响应于Ag加LPS而在更大程度上积累。这些结果表明，佐剂通过可以在不存在IL-2的情况下起作用的CD 28依赖性信号改善体内T细胞增殖。
The adoptive transfer of naive CD4+ T cell receptor (TCR) transgenic T cells was used to investigate the mechanisms by which the adjuvant lipopolysaccharide (LPS) enhance T cell clonal expansion in vivo. Subcutaneous administration of soluble antigen (Ag) resulted in rapid and transient accumulation of the Ag-specific T cells in the draining lymph nodes (LNs), which was preceded by the production of interleukin (IL)-2. CD28-deficient, Ag-specific T cells produced only small amounts of IL-2 in response to soluble Ag and did not accumulate in the LN to the same extent as wild-type T cells. Injection of Ag and LPS, a natural immunological adjuvant, enhanced IL-2 production and LN accumulation of wild-type, Ag-specific T cells but had no significant effect on CD28-deficient, Ag-specific T cells. Therefore, CD28 is critical for Ag-driven IL-2 production and T cell proliferation in vivo, and is essential for the LPS-mediated enhancement of these events. However, enhancement of IL-2 production could not explain the LPS-dependent increase of T cell accumulation because IL-2–deficient, Ag-specific T cells accumulated to a greater extent in the LN than wild-type T cells in response to Ag plus LPS. These results indicate that adjuvants improve T cell proliferation in vivo via a CD28-dependent signal that can operate in the absence of IL-2.
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DOI：
10.1084/jem.182.5.1357
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Openshaw P;Murphy EE;Hosken NA;Maino V;Davis K;Murphy K;O'Garra A
通讯作者：
O'Garra A
影响因子：
4.4
作者：
LIU, Y;JANEWAY, CA
通讯作者：
JANEWAY, CA
影响因子：
4.4
作者：
POWRIE, F;LEACH, MW;COFFMAN, RL
通讯作者：
COFFMAN, RL
影响因子：
2.2
作者：
REINER, SL;ZHENG, SC;LOCKSLEY, RM
通讯作者：
LOCKSLEY, RM
小鼠B7-2 costimulator的组织分布：在原位和体外成熟期间在树突状细胞上表达丰富的表达。
影响因子：
15.3
作者：
Inaba, K.;Witmer-Pack, M.;Inaba, M.;Hathcock, K. S.;Sakuta, H.;Azuma, M.;Yagita, H.;Okumura, K.;Linsley, P. S.;Ikehara, S.;Muramatsu, S.;Hodes, R. J.;Steinman, R. M.
通讯作者：
Steinman, R. M.