关键词: CD4 T cell SARS‐CoV‐2 cTFH coronavirus hCoV lymph node

来  源:   DOI:10.1002/cti2.1264   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
OBJECTIVE: Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults.
METHODS: We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals. Antigen-specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation-induced marker assay and characterised for memory phenotype and chemokine receptor expression.
RESULTS: T-cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung-draining lymph nodes.
CONCLUSIONS: Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.
摘要:
目的:地方性人类冠状病毒(hCoV)在世界范围内传播,但死亡率最低。尽管在儿童时期血清转化为hCoV几乎无处不在,对成人hCoV特异性T细胞记忆知之甚少。
方法:我们定量了42个SARS-CoV-2未感染个体对hCoV刺突抗原的CD4T细胞和抗体反应。使用活化诱导的标记物测定法鉴定抗原特异性记忆T细胞和循环滤泡辅助T细胞(cTFH),并表征记忆表型和趋化因子受体表达。
结果:T细胞反应在常规记忆和cTFH区室中广泛存在,但与IgG滴度无关。在48%的参与者中观察到SARS-CoV-2交叉反应性T细胞,并与HKU1记忆相关。hCoV特异性T细胞在血液中表现出CCR6+中枢记忆表型,但在人肺引流淋巴结中的频率和CXCR3表达富集。
结论:总体而言,hCoV特异性体液和细胞记忆独立维持,在冠状病毒特异性CD4T细胞中存在共同的表型。对地方性冠状病毒免疫的这种理解提供了对免疫反应的稳态维持的见解,这可能是预防SARS-CoV-2的关键组成部分。
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