Acellular Pertussis Vaccines Induce CD8+ and CD4+ Regulatory T Cells That Suppress Protective Tissue-Resident Memory CD4+ T Cells, in Part via IL-10

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Caitlín Ní Chasaide, Pauline Schmitt, Béré K. Diallo, Lisa Borkner, Charlotte M. Leane, Seyed Davoud Jazayeri, Sreeram Udayan, Eoin O'Neill, Lucy M. Curham, Barry Moran, Mieszko M. Wilk, Kingston H. G. Mills
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Abstract

Tissue-resident memory T (TRM) cells play a key role in sustained protective immunity against Bordetella pertussis infection of the nasal mucosa. Current alum-adjuvanted acellular pertussis (aP) vaccines protect against severe pertussis disease but fail to prevent nasal infection with B. pertussis. Here we demonstrate that immunization of mice with an aP vaccine failed to generate respiratory TRM cells, but did induce antigen-specific CD4+ Treg cells that expressed Foxp3, CD49b, PD-1 and LAG-3, and CD8+ Treg cells that expressed CD122, PD-1, and IL-10. B. pertussis-specific CD4+ and CD8+ T cell lines established from aP-immunized mice expressed the regulatory markers and suppressed activation of Th1 and Th17 cells. Blockade of IL-10 signaling during aP immunization or B. pertussis challenge promoted the induction of IL-17-secreting CD4+ TRM responses and enhanced bacterial clearance from the nose. Addition of the adjuvant LP-GMP, comprising TLR2 and STING agonists, to the aP vaccine and delivery by the nasal route promoted the induction of antigen-specific IL-17-producing CD4+ TRM cells and enhanced vaccine efficacy. Our findings demonstrate that aP vaccines suppress the induction of protective TRM cells in part through the induction of CD4+ and CD8+ Treg cells, which can be overcome using a potent adjuvant and delivery of the vaccine intranasally.

Abstract Image

无细胞百日咳疫苗诱导CD8+和CD4+调节性T细胞抑制保护性组织驻留记忆CD4+ T细胞,部分通过IL-10
组织驻留记忆T (TRM)细胞在抗百日咳杆菌感染的鼻黏膜持续保护性免疫中起关键作用。目前的铝佐剂无细胞百日咳(aP)疫苗可以预防严重的百日咳疾病,但不能预防百日咳B.鼻腔感染。本研究证明,用aP疫苗免疫小鼠不能产生呼吸道TRM细胞,但可以诱导表达Foxp3、CD49b、PD-1和LAG-3的抗原特异性CD4+ Treg细胞,以及表达CD122、PD-1和IL-10的CD8+ Treg细胞。由ap免疫小鼠建立的百日咳特异性CD4+和CD8+ T细胞系表达调节标记物并抑制Th1和Th17细胞的激活。在aP免疫或百日咳攻击期间,阻断IL-10信号传导可促进il -17分泌CD4+ TRM反应的诱导,并增强鼻腔细菌清除。将含有TLR2和STING激动剂的LP-GMP佐剂添加到aP疫苗中并经鼻途径给药,可诱导产生抗原特异性il -17的CD4+ TRM细胞,增强疫苗效力。我们的研究结果表明,aP疫苗部分通过诱导CD4+和CD8+ Treg细胞来抑制保护性TRM细胞的诱导,这可以通过有效的佐剂和鼻内给药来克服。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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