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CD70-expressing CD4 T cells produce IFN-γ and IL-17 in rheumatoid arthritis
Park, Jin Kyun,Han, Bobby Kwanghoon,Park, Ji Ah,Woo, Youn Jung,Kim, So Young,Lee, Eun Young,Lee, Eun Bong,Chalan, Paulina,Boots, Annemieke M.,Song, Yeong Wook Oxford University Press 2014 Rheumatology Vol.53 No.10
<P><B>Objective.</B> CD70-expressing CD4 T cells are enriched in RA and promote autoimmunity via co-stimulatory CD70-CD27 interaction. This study aimed to explore the phenotype and cytokine production of CD70<SUP>+</SUP> CD4 T cells in RA.</P><P><B>Methods.</B> Peripheral blood mononuclear cells from 32 RA patients were isolated and frequencies of CD70<SUP>+</SUP> cells within different CD4 T subsets were analysed using flow cytometry. IFN-γ and IL-17 production were compared between the CD70<SUP>+</SUP> and CD70<SUP>−</SUP> cells. Expression of master transcription factors T-bet, GATA3 and retinoic acid–related orphan receptor gamma t (RORγt) were examined by real-time PCR. Results are presented as mean (<SMALL>s.e.m</SMALL>.).</P><P><B>Results.</B> CD4 T cells of healthy controls rarely expressed CD70 as compared with CD4 T cells of RA patients [mean 0.9% (<SMALL>s.e.m</SMALL>. 0.3%) <I>vs</I> 7.6 (0.6), <I>P</I> < 0.001]. In RA, CD70<SUP>+</SUP> cells were present within all CD4 T cell subsets, i.e. CD45RA<SUP>+</SUP>CCR7<SUP>+</SUP> naive, CD45RA<SUP>−</SUP>CCR7<SUP>+</SUP> central memory, CD45RA<SUP>−</SUP>CCR7<SUP>−</SUP> effector memory and CD45RA<SUP>+</SUP>CCR7<SUP>−</SUP> terminally differentiated effector memory T cells with a mean frequency of 3.9% (<SMALL>s.e.m</SMALL>. 1.1%), 4.0 (0.5), 4.2 (0.7) and 9.4 (4.3), respectively. As compared to CD70<SUP>−</SUP> CD4 T cells, CD70<SUP>+</SUP> CD4 T cells produced significantly more IFN-γ and IL-17 after short activation. CD70<SUP>+</SUP> CD4 T cells preferentially expressed transcription factor RORγt.</P><P><B>Conclusion.</B> CD70<SUP>+</SUP> CD4 T cells are enriched in RA and may directly contribute to RA pathogenesis by producing IFN-γ and IL-17. Targeting CD70<SUP>+</SUP> CD4 T cells might offer new therapeutic opportunities in RA.</P>