Extrafollicular PD-1highCXCR5-CD4+ T cells participate in local immunoglobulin production in nasal polyps.
J Allergy Clin Immunol
; 149(2): 610-623, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34224786
ABSTRACT
BACKGROUND:
Local immunoglobulin hyperproduction is observed in nasal polyps (NPs) with and without ectopic lymphoid tissues (eLTs).OBJECTIVE:
Our aim was to identify the T-cell subsets involved in local immunoglobulin production independent of eLTs in NPs.METHODS:
The localization, abundance, and phenotype of CD4+ T-cell subsets were studied by immunofluorescence, flow cytometry, and single-cell RNA sequencing. Purified nasal T-cell subsets were cultured with autologous peripheral naive B cells to explore their function. Programmed death ligand 1 and programmed death ligand 2 expression in NPs was investigated by immunofluorescence staining and flow cytometry.RESULTS:
Accumulation of PD-1highCXCR5-CD4+ T cells outside lymphoid aggregates was found in NPs. Nasal PD-1highCXCR5-CD4+ T cells were characterized by a unique phenotype that was related to B-cell help and tissue residency and distinct from PD-1-/intCXCR5- and CXCR5+ CD4+ T cells in NPs as well as PD-1highCXCR5highCD4+ follicular helper T cells in tonsils. Compared with the frequencies of PD-1highCXCR5-CD4+ T cells and their IFN-γ+, IL-17A+, and IL-21+ subsets in the control inferior turbinate tissues, the frequencies of these cells and their subsets were increased in both eosinophilic and noneosinophilic NPs, whereas the frequencies of the IL-4+ and IL-4+IL-21+ subsets were increased only in eosinophilic NPs. Nasal PD-1highCXCR5-CD4+ T cells induced immunoglobulin production from B cells in a potency comparable to that induced by tonsillar follicular helper T cells. PD-1highCXCR5-CD4+ T-cell frequencies were correlated with IgE levels in eosinophilic NPs. PD-L1 and PD-L2 suppressed the function of PD-1highCXCR5-CD4+ T cells, and their levels were reduced in NPs. PD-1highCXCR5-CD4+ T-cell abundance was associated with the postsurgical relapse of NPs.CONCLUSION:
PD-1highCXCR5-CD4+ T cells participate in local immunoglobulin production independent of eLTs in NPs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulinas
/
Linfócitos T CD4-Positivos
/
Pólipos Nasais
/
Receptores CXCR5
/
Receptor de Morte Celular Programada 1
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China