title: Human lymph-node CD8(+) T cells display an altered phenotype during systemic autoimmunity.
abstract: Although many studies are focused on auto-reactive CD4(+) T cells, the precise role of CD8(+) T cells in autoimmunity is poorly understood. The objective of this study is to provide more insight into the phenotype and function CD8(+) T cells during the development of autoimmune disease by studying CD8(+) T cells in human lymph-node biopsies and peripheral blood obtained during the earliest phases of rheumatoid arthritis (RA). Here, we show that lymphoid pro-inflammatory CD8(+) T cells exhibit a less-responsive phenotype already during the earliest phases of autoimmunity compared with healthy individuals. We found an increase in CD8(+) memory T cells in lymphoid tissue during the earliest phases of autoimmunity, even before clinical onset of RA, accompanied by an increased frequency of non-circulating or recently activated (CD69(+)) CD8(+) T cells in lymphoid tissue and peripheral blood. Importantly, lymphoid pro-inflammatory CD8(+)IL-17A(+) T cells displayed a decreased capacity of cytokine production, which was related to disease activity in early RA patients. In addition, a decreased frequency of regulatory CD8(+)IL-10(+) T cells in peripheral blood was also related to disease activity in early RA patients. Our results suggest that different CD8(+) T-cell subsets are affected already during the earliest phases of systemic autoimmunity.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tamara H
authors.initials: TH
authors.lastname: Ramwadhdoebe
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Hähnlein
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bo J
authors.initials: BJ
authors.lastname: van Kuijk
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center/University of Amsterdam , Amsterdam, The Netherlands.
authors.forename: Ivy Y
authors.initials: IY
authors.lastname: Choi
authors.affiliation: Department of Radiology, Academic Medical Center/University of Amsterdam , Amsterdam, The Netherlands.
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: van Boven
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Clinical Unit Cambridge, GlaxoSmithKline, Cambridge, UK.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; University of Cambridge, Cambridge, UK; Ghent University, Ghent, Belgium; GlaxoSmithKline, Stevenage, UK.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center (ARC), Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: van Baarsen