CD20 positive CD8 T cells are a unique and transcriptionally-distinct subset of T cells with distinct transmigration properties

被引:25
作者
Vlaming, Martijn [1 ]
Bilemjian, Vrouyr [1 ]
Freile, Jimena Alvarez [1 ]
Lourens, Harm Jan [1 ]
van Rooij, Nienke [2 ]
Huls, Gerwin [1 ]
van Meerten, Tom [1 ]
de Bruyn, Marco [2 ]
Bremer, Edwin [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands
关键词
EFFECTOR; RITUXIMAB; LYMPHOCYTES; EXPRESSION; LOCALIZATION; CADHERIN; DISEASE; PROTEIN; IMPACT; BLOOD;
D O I
10.1038/s41598-021-00007-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The presence of T cells that are dimly positive for the B cell marker CD20 is well-established in autoimmunity and correlates with disease severity in various diseases. Further, we previously identified that the level of CD20-positive T cells was three-fourfold elevated in ascites fluid of ovarian carcinoma patients, together suggesting a role in both autoimmunity and cancer. In this respect, treatment of autoimmune patients with the CD20-targeting antibody Rituximab has also been shown to target and deplete CD20-positive T cells, previously identified as IFN-gamma producing, low proliferative, CD8 cytotoxic T cells with an effector memory (EM) differentiation state. However, the exact phenotype and relevance of CD20-positive T cells remains unclear. Here, we set out to identify the transcriptomic profile of CD20-positive T cells using RNA sequencing. Further, to gain insight into potential functional properties of CD20 expression in T cells, CD20 was ectopically expressed on healthy human T cells and phenotypic, functional, migratory and adhesive properties were determined in vitro and in vivo. Together, these assays revealed a reduced transmigration and an enhanced adhesive profile combined with an enhanced activation status for CD20-positive T cells.
引用
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页数:13
相关论文
共 57 条
[41]   IFIT2 Is an Effector Protein of Type I IFN-Mediated Amplification of Lipopolysaccharide (LPS)-Induced TNF-α Secretion and LPS-Induced Endotoxin Shock [J].
Siegfried, Alexandra ;
Berchtold, Susanne ;
Manncke, Birgit ;
Deuschle, Eva ;
Reber, Julia ;
Ott, Thomas ;
Weber, Michaela ;
Kalinke, Ulrich ;
Hofer, Markus J. ;
Hatesuer, Bastian ;
Schughart, Klaus ;
Gailus-Durner, Valerie ;
Fuchs, Helmut ;
de Angelis, Martin Hrabe ;
Weber, Friedemann ;
Hornef, Mathias W. ;
Autenrieth, Ingo B. ;
Bohn, Erwin .
JOURNAL OF IMMUNOLOGY, 2013, 191 (07) :3913-3921
[42]  
Storie I, 1995, CLIN LAB HAEMATOL, V17, P323
[43]   Cow's milk-specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10 [J].
Tiemessen, MM ;
Van Leperen-Van Dijk, AG ;
Bruijnzeel-Koomen, CAFM ;
Garssen, J ;
Knol, EF ;
Van Hoffen, E .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2004, 113 (05) :932-939
[44]   Complex memory T-cell phenotypes revealed by coexpression of CD62L and CCR7 [J].
Unsoeld, H ;
Pircher, H .
JOURNAL OF VIROLOGY, 2005, 79 (07) :4510-4513
[45]   Complement-induced cell death by rituximab depends on CD20 expression level and acts complementary to antibody-dependent cellular cytotoxicity [J].
van Meerten, Tom ;
van Rijn, Rozemarijn S. ;
Hol, Samantha ;
Hagenbeek, Anton ;
Ebeling, Saskia B. .
CLINICAL CANCER RESEARCH, 2006, 12 (13) :4027-4035
[46]   CD20-Targeted Therapy: The Next Generation of Antibodies [J].
van Meerten, Tom ;
Hagenbeek, Anton .
SEMINARS IN HEMATOLOGY, 2010, 47 (02) :199-210
[47]   Quantitative assessment of human T lymphocytes in RAG2-/- γc mice:: The impact of ex vivo manipulation on in vivo functionality [J].
van Rijn, Rozemarijn S. ;
Simonetti, Elles R. ;
Hagenbeek, Anton ;
Bonyhadi, Mark ;
Storm, Gert ;
Martens, Anton C. M. ;
Ebeling, Saskia B. .
EXPERIMENTAL HEMATOLOGY, 2007, 35 (01) :117-127
[48]   A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- γc-/- double-mutant mice [J].
van Rijn, RS ;
Simonetti, ER ;
Hagenbeek, A ;
Hogenes, MCH ;
de Weger, RA ;
Canninga-van Dijk, MR ;
Weijer, K ;
Spits, H ;
Storm, G ;
van Bloois, L ;
Rijkers, G ;
Martens, ACM ;
Ebeling, SB .
BLOOD, 2003, 102 (07) :2522-2531
[49]   Proinflammatory CD20+ T cells in the pathogenesis of multiple sclerosis [J].
von Essen, Marina R. ;
Ammitzboll, Cecilie ;
Hansen, Rikke H. ;
Petersen, Eva R. S. ;
McWilliam, Oskar ;
Marquart, Hanne V. ;
Damm, Peter ;
Sellebjerg, Finn .
BRAIN, 2019, 142 :120-132
[50]   L-Selectin Enhanced T Cells Improve the Efficacy of Cancer Immunotherapy [J].
Watson, H. Angharad ;
Durairaj, Ruban R. P. ;
Ohme, Julia ;
Alatsatianos, Markella ;
Almutairi, Hanan ;
Mohammed, Rebar N. ;
Vigar, Miriam ;
Reed, Sophie G. ;
Paisey, Stephen J. ;
Marshall, Christopher ;
Gallimore, Awen ;
Ager, Ann .
FRONTIERS IN IMMUNOLOGY, 2019, 10