Human PD-1hiCD8+ T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis.
Front Immunol
; 12: 654623, 2021.
Article
em En
| MEDLINE
| ID: mdl-33815416
ABSTRACT
Background:
Rheumatoid arthritis (RA) is a prototypical autoantibody-driven autoimmune disease in which T-B interactions play a critical role. Recent comprehensive analysis suggests that PD-1+CD8+ T cells as well as two distinct IL-21-producing PD-1+CD4+ T cell subsets, follicular helper T (Tfh) and peripheral helper T (Tph) cells, are involved in the pathogenesis of RA. Herein, we aimed to clarify a generation mechanism of IL-21-producing CD8+ T cells in humans, and to characterize this novel subset in patients with RA.Methods:
CD8+ T cells in the peripheral blood (PB) and synovial fluid (SF) of healthy control (HC) and patients with RA were subject to the analysis of IL-21 mRNA and protein. We evaluated the surface marker, cytokine and transcription profiles of IL-21-producing CD8+ T cells in HCPB, RAPB and RASF.Results:
IL-21-producing CD8+ T cells were enriched in the CD45RA-(memory) PD-1+, especially PD-1hi subpopulation, and IL-12 and IL-21 synergistically induced IL-21 production by naïve CD8+ T cells. Memory PD-1hiCD8+ T cells in HCPB facilitated plasmablast differentiation and IgG production in an IL-21-dependent manner. In addition, PD-1hiCD8+ T cells in RASF and RAPB produced large amounts of IL-21 and were characterized by high levels of CD28, ICOS, CD69, HLA-DR, and CCR2 but not CXCR5. Furthermore, PD-1hiCD8+ T cells expressed high levels of transcripts of MAF and PRDM1, a feature observed in Tph cells.Conclusions:
Identification of IL-21-producing PD-1hiCD8+ T cells expands our knowledge of T cell subsets with B helper functions in RA. Selective targeting of these subsets could pave an avenue for the development of novel treatment strategies for this disease.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Interleucinas
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Linfócitos T CD8-Positivos
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Receptor de Morte Celular Programada 1
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article