Qualitative changes accompany memory T cell generation: Faster, more effective responses at lower doses of antigen

Qualitative changes accompany memory T cell generation: Faster, more effective responses at lower doses of antigen
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DOI:
10.4049/jimmunol.164.5.2338
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发表时间:
2000-03-01
影响因子:
4.4
通讯作者:
Swain, SL
Swain, SL
中科院分区:
医学2区
文献类型:
--
作者:
Rogers, PR;Dubey, C;Swain, SL

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记忆T细胞的产生对于免疫系统之前遇到的病原体的快速清除和中和至关重要。我们研究了CD 4(+)记忆T细胞增殖和细胞因子分泌的反应动力学和Ag剂量要求,以检查是否存在可能导致免疫力改善的质的变化。TCR Tg CD 4(+)T细胞在体外引发并转移到T细胞缺陷型宿主中。6周或更长时间后,持续存在的T细胞仅为具有记忆表型的小静息细胞:CD 44(高)CD 62 L(+/-)CD 25(-)。记忆性CD 4 T细胞表现出与幼稚细胞相似的对肽类似物的应答模式,所述肽类似物具有相似的IL-2分泌的Ag剂量要求。然而,记忆细胞(来源于Th 2和Th 1效应子)显示出更快的细胞因子分泌、细胞分裂和增殖动力学,响应于低剂量的Ag或肽类似物而增强的增殖,以及IL-4、IL-5和IFN-γ的产生,这些结果表明,CD 4记忆T细胞对Ag的反应要有效得多。此外,研究人员还发现,记忆细胞的功能能力扩大,将促进效应功能的快速发展,提供更快速和有效的免疫力。
The generation of memory T cells is critically important for rapid clearance and neutralization of pathogens encountered previously by the immune system. We have studied the kinetics of response and Ag dose requirements for proliferation and cytokine secretion of CD4(+) memory T cells to examine whether there are qualitative changes which might lead to improved immunity. TCR Tg CD4(+) T cells were primed in vitro and transferred into T cell-deficient hosts, After 6 or more weeks, the persisting T cells were exclusively small resting cells with a memory phenotype: CD44(high) CD62L(+/-) CD25(-). Memory CD4 T cells showed a similar pattern of response as naive cells to peptide analogues with similar Ag dose requirements for IL-2 secretion. However, memory cells (derived from both Th2 and Th1 effectors) displayed faster kinetics of cytokine secretion, cell division, and proliferation, enhanced proliferation in response to low doses of Ag or peptide analogues, and production of IL-4, IL-5, and IFN-gamma, These results suggest there is a much more efficient response of CD4 memory T cells to Ag re-exposure and that the expanded functional capacity of memory cells will promote a rapid development of effector functions, providing more rapid and effective immunity.