Nuclear antigen-reactive CD4+ T cells expand in active systemic lupus erythematosus, produce effector cytokines, and invade the kidneys

被引：27

作者：

Abdirama, Dimas ^{[1
,2
,3
,4
,5
]}

Tesch, Sebastian ^{[1
,2
,3
,4
,5
]}

Griessbach, Anna-Sophie ^{[1
,2
,3
,4
,5
]}

von Spee-Mayer, Caroline ^{[6
]}

Humrich, Jens Y. ^{[7
]}

Stervbo, Ulrik ^{[8
,9
]}

Babel, Nina ^{[8
,9
]}

Meisel, Christian ^{[10
,11
]}

Alexander, Tobias ^{[1
,2
,3
,4
]}

Biesen, Robert ^{[1
,2
,3
,4
]}

Bacher, Petra ^{[1
,2
,3
,4
,5
]}

Scheffold, Alexander ^{[1
,2
,3
,4
,5
]}

Eckardt, Kai-Uwe ^{[12
]}

Hiepe, Falk ^{[1
,2
,3
,4
]}

Radbruch, Andreas ^{[5
]}

Burmester, Gerd-Rudiger ^{[1
,2
,3
,4
]}

Riemekasten, Gabriela ^{[7
]}

Enghard, Philipp ^{[12
]}

机构：

[1] Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany

[2] Free Univ Berlin, Berlin, Germany

[3] Humboldt Univ, Berlin, Germany

[4] Berlin Inst Hlth, Berlin, Germany

[5] Deutsch Rheuma Forschungszentrum, Berlin, Germany

[6] Univ Freiburg, Fac Med, Med Ctr, Ctr Chron Immunodeficiency, Freiburg, Germany

[7] Univ Klinikum Schleswig Holstein, Dept Rheumatol & Clin Immunol, Ratzeburger Allee 160, D-23538 Lubeck, Germany

[8] Berlin Brandenburg Ctr Regenerat Therapie, Berlin, Germany

[9] Ruhr Univ Bochum, Univ Klinikum, Ctr Translat Med, Bochum, Germany

[10] Charite Univ Med Berlin, Inst Med Immunol, Berlin, Germany

[11] Charite Vivantes GmbH, Lab Berlin, Berlin, Germany

[12] Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Augustenburger Pl 1, D-13353 Berlin, Germany

来源：

KIDNEY INTERNATIONAL | 2021年 / 99卷 / 01期

关键词：

autoreactive T cells; lupus nephritis; SLE; HUMAN NAIVE; IFN-GAMMA; NEPHRITIS; REPERTOIRE; AUTOANTIGEN; FREQUENCY; GLOMERULONEPHRITIS; PROTEIN;

D O I：

10.1016/j.kint.2020.05.051

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4(+) T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4(+) T cells has been extremely challenging. Here we present an analysis of CD4(+) T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigenreactive T cell enrichment. The frequencies of nuclear antigen specific CD4(+) T cells correlated with disease severity. These autoreactive T cells produce effector cytokines such as interferon-gamma, interleukin-17, and interleukin-10. Compared to blood, these cells were enriched in the urine of patients with active lupus nephritis, suggesting an infiltration of the inflamed kidneys. Thus, these previously unrecognized characteristics support a role for nuclear antigen-specific CD4(+) T cells in systemic lupus erythematosus.

引用

页码：238 / 246

页数：9

共 38 条

[1] The immune cell landscape in kidneys of patients with lupus nephritis [J].

Arazi, Arnon ;

Rao, Deepak A. ;

Berthier, Celine C. ;

Davidson, Anne ;

Liu, Yanyan ;

Hoover, Paul J. ;

Chicoine, Adam ;

Eisenhaure, Thomas M. ;

Jonsson, A. Helena ;

Li, Shuqiang ;

Lieb, David J. ;

Zhang, Fan ;

Slowikowski, Kamil ;

Browne, Edward P. ;

Noma, Akiko ;

Sutherby, Danielle ;

Steelman, Scott ;

Smilek, Dawn E. ;

Tosta, Patti ;

Apruzzese, William ;

Massarotti, Elena ;

Dall'Era, Maria ;

Park, Meyeon ;

Kamen, Diane L. ;

Furie, Richard A. ;

Payan-Schober, Fernanda ;

Pendergraft, William F., III ;

McInnis, Elizabeth A. ;

Buyon, Jill P. ;

Petri, Michelle A. ;

Putterman, Chaim ;

Kalunian, Kenneth C. ;

Woodle, E. Steve ;

Lederer, James A. ;

Hildeman, David A. ;

Nusbaum, Chad ;

Raychaudhuri, Soumya ;

Kretzler, Matthias ;

Anolik, Jennifer H. ;

Brenner, Michael B. ;

Wofsy, David ;

Hacohen, Nir ;

Diamond, Betty ;

Waguespack, Dia ;

Connery, Sean M. ;

McMahon, Maureen A. ;

McCune, William J. ;

Kado, Ruba B. ;

Hsu, Raymond ;

Cunningham, Melissa A. .

NATURE IMMUNOLOGY, 2019, 20 (07) :902-+

[2] Development of autoantibodies before the clinical onset of systemic lupus erythematosus [J].

Arbuckle, MR ;

McClain, MT ;

Rubertone, MV ;

Scofield, RH ;

Dennis, GJ ;

James, JA ;

Harley, JB .

NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (16) :1526-1533

[3]

Bacher P, 2013, CYTOM PART A, V83A, P692, DOI [10.1002/cyto.22317, 10.1002/cyto.a.22317]

[4] Antigen-Reactive T Cell Enrichment for Direct, High-Resolution Analysis of the Human Naive and Memory Th Cell Repertoire [J].

Bacher, Petra ;

Schink, Christian ;

Teutschbein, Janka ;

Kniemeyer, Olaf ;

Assenmacher, Mario ;

Brakhage, Axel A. ;

Scheffold, Alexander .

JOURNAL OF IMMUNOLOGY, 2013, 190 (08) :3967-3976

[5] INTERSTITIAL IMMUNE-COMPLEX NEPHRITIS IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS [J].

BRENTJENS, JR ;

SEPULVEDA, M ;

BALIAH, T ;

BENTZEL, C ;

ERLANGER, BF ;

ELWOOD, C ;

MONTES, M ;

HSU, KC ;

ANDRES, GA .

KIDNEY INTERNATIONAL, 1975, 7 (05) :342-350

[6] AUTOANTIGENS TARGETED IN SYSTEMIC LUPUS-ERYTHEMATOSUS ARE CLUSTERED IN 2 POPULATIONS OF SURFACE-STRUCTURES ON APOPTOTIC KERATINOCYTES [J].

CASCIOLAROSEN, LA ;

ANHALT, G ;

ROSEN, A .

JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (04) :1317-1330

[7] AUTOANTIGEN-SPECIFIC T-CELL PROLIFERATION INDUCED BY THE RIBOSOMAL P2 PROTEIN IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS [J].

CROW, MK ;

DELGIUDICEASCH, G ;

ZEHETBAUER, JB ;

LAWSON, JL ;

BROT, N ;

WEISSBACH, H ;

ELKON, KB .

JOURNAL OF CLINICAL INVESTIGATION, 1994, 94 (01) :345-352

[8] TCR Repertoire Analysis by Next Generation Sequencing Allows Complex Differential Diagnosis of T Cell-Related Pathology [J].

Dziubianau, M. ;

Hecht, J. ;

Kuchenbecker, L. ;

Sattler, A. ;

Stervbo, U. ;

Roedelsperger, C. ;

Nickel, P. ;

Neumann, A. U. ;

Robinson, P. N. ;

Mundlos, S. ;

Volk, H-D ;

Thiel, A. ;

Reinke, P. ;

Babel, N. .

AMERICAN JOURNAL OF TRANSPLANTATION, 2013, 13 (11) :2842-2854

[9] CXCR3+CD4+T Cells Are Enriched in Inflamed Kidneys and Urine and Provide a New Biomarker for Acute Nephritis Flares in Systemic Lupus Erythematosus Patients [J].

Enghard, P. ;

Humrich, J. Y. ;

Rudolph, B. ;

Rosenberger, S. ;

Biesen, R. ;

Kuhn, A. ;

Manz, R. ;

Hiepe, F. ;

Radbruch, A. ;

Burmester, G. -R. ;

Riemekasten, G. .

ARTHRITIS AND RHEUMATISM, 2009, 60 (01) :199-206

[10] Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response [J].

Enghard, Philipp ;

Rieder, Claudia ;

Kopetschke, Katharina ;

Klocke, J. R. ;

Undeutsch, Reinmar ;

Biesen, Robert ;

Dragun, Duska ;

Gollasch, Maik ;

Schneider, Udo ;

Aupperle, Karlfried ;

Humrich, Jens Y. ;

Hiepe, Falk ;

Backhaus, Marina ;

Radbruch, A. H. ;

Burmester, Gerd R. ;

Riemekasten, Gabriela .

ANNALS OF THE RHEUMATIC DISEASES, 2014, 73 (01) :277-283

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