Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific

Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific
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DOI:
10.1182/blood-2005-08-3255
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发表时间:
2006-04-01
期刊:
影响因子:
20.3
通讯作者:
Stevenson, FK
Stevenson, FK
中科院分区:
医学1区
文献类型:
--
作者:
Di Genova, G;Roddick, J;Stevenson, FK

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人类受试者对感染性生物体保持长期免疫记忆,但机制尚不清楚。CD 4(+)T辅助记忆(Th-Th)细胞在控制体液和细胞反应中起关键作用,因此它们的寿命和对疫苗接种的反应对于维持保护性免疫至关重要。为了探索Th细胞对抗原攻击的反应动力学,我们调查了破伤风类毒素(TT)加强注射后的受试者。TT特异性Th-NK细胞的扩增和细胞因子的产生显示出复杂的动力学。引人注目的是,平行的扩增和细胞因子的产生发生在预先存在的特异于另外两种常见抗原的Thrombus细胞中:结核菌素和白色念珠菌的纯化蛋白衍生物。旁观者扩增发生在Th细胞中,但在Th-幼稚细胞中没有。抗TT抗体产生在接种后约2周达到峰值,并逐渐下降。然而,针对其他抗原的预先存在的抗体没有改变。似乎尽管所有的Th细胞都容易被刺激扩增,但抗体应答受抗原可用性控制。这些发现与记忆的维持有关,并对评估特定T细胞对疫苗接种的反应产生影响。
Human subjects maintain long-term immunologic memory against infective organisms but the mechanism is unclear. CD4(+) T-helper memory (Th-mem) cells are pivotal in controlling humoral and cellular responses, therefore their longevity and response to vaccination are critical for maintenance of protective immunity. To probe the dynamics of the Th-mem-cell response to antigenic challenge, we investigated subjects following a booster injection with tetanus toxoid (TT). Expansion of TT-specific Th-mem cells and cytokine production showed complex kinetics. Strikingly, parallel expansion and cytokine production occurred in pre-existing Thmem cells specific for 2 other common antigens: purified protein derivative of tuberculin and Candida albicans. Bystander expansion occurred in Thmem but not in Th-naive cells. Antibody production against TT peaked approximately 2 weeks after vaccination and gradually declined. However, pre-existing antibody against the other antigens did not change. It appears that although all Thmem cells are readily stimulated to expand, antibody responses are controlled by antigen availability. These findings relate to the maintenance of memory and have consequences for assessments of specific T-cell responses to vaccination.