Human TCR α/β+ CD4-CD8- double-negative T cells in patients with autoimmune lymphoproliferative syndrome express restricted Vβ TCR diversity and are clonally related to CD8+ T cells

被引:57
作者
Bristeau-Leprince, Anne [1 ,2 ]
Mateo, Veronique [3 ]
Lim, Annick [1 ,2 ]
Magerus-Chatinet, Aude [3 ]
Solary, Eric [4 ]
Fischer, Alain [3 ]
Rieux-Laucat, Frederic [3 ]
Gougeon, Marie-Lise [1 ,2 ]
机构
[1] Inst Pasteur, Antiviral Immun Biotherapy & Vaccine Unit, Infect & Epidemiol Dept, F-75725 Paris 15, France
[2] INSERM, U668, Paris, France
[3] Univ Paris 05, Hop Necker Enfants Malad, INSERM, U768, Paris, France
[4] Univ Burgundy, Ctr Hosp Univ, IFR 100, UMR,INSERM,U866, Dijon, France
关键词
D O I
10.4049/jimmunol.181.1.440
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The peripheral expansion of alpha/beta(+)-CD4(-)CD8(-) double negative (DN) T cells in patients with autoimmune lymphoproliferative syndrome (ALPS) is a consistent feature of this disease, and part of the diagnostic criteria of ALPS. The origin of these cells remains undetermined. They could derive from mature T cells that have lost coreceptor expression, or represent a special minor cell lineage. To investigate relationship of DN and single positive (SP) T cells in ALPS, we used Immunoscope technology to analyze the TCRV beta repertoire diversity of sorted DN and SP T cells, and we performed CDR3 sequence analyses of matching clonotypes. We show that DN T cells express all the V beta gene families that are used by their SP counterparts, though they dominantly use some V beta genes. Analysis of CDR3 length distribution revealed a diverse polyclonal TCR repertoire for sorted CD4(+) T cells, whereas both DN and CD8(+) T cells showed a skewed TCR repertoire with oligoclonal expansions throughout most of the V beta families. CDR3 sequencing of matching clonotypes revealed a significant sharing of CDR3 sequences from selected V beta-J beta transcripts between DN and CD8(+) T cells. Altogether, these data strongly argue for a CD8 origin of DN T cells in ALPS.
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收藏
页码:440 / 448
页数:9
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