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

Autor: Alain Fischer, Véronique Mateo, Eric Solary, Marie-Lise Gougeon, Aude Magerus-Chatinet, Annick Lim, Anne Bristeau-Leprince, Frédéric Rieux-Laucat
Přispěvatelé: Immunité Antivirale, Biothérapie et Vaccins, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 6th FP STREP Autorome Consortium, 'From Immune Responses in Rare Autoimmune Diseases to Novel Therapeutic Intervention Strategies' LSHM-CT-2004-005264, ANR-05-MRAR-0017,ALPS Study,Syndrome lymphoprolifératif avec autoimmunité : défauts génétiques de l'apoptose lymphocytaire chez l'homme(2005), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), ANR no. 05-MRAR-017,ANR no. 05-MRAR-017, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2008
Předmět:
Male
Transcription
Genetic
Receptors
Antigen
T-Cell
alpha-beta
T-Lymphocytes
Apoptosis
Cell Separation
Autoantigens
Interleukin 21
0302 clinical medicine
Sequence Analysis
Protein
[ SDV.IMM ] Life Sciences [q-bio]/Immunology
Immunology and Allergy
Cytotoxic T cell
Child
double negative T cells
0303 health sciences
Repertoire
hemic and immune systems
3. Good health
Phenotype
Child
Preschool
CD4 Antigens
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Adult
CD8 Antigens
Molecular Sequence Data
Immunology
Double negative
chemical and pharmacologic phenomena
Biology
Autoimmune Diseases
Fas/CD95
03 medical and health sciences
medicine
Humans
Amino Acid Sequence
Gene
030304 developmental biology
Base Sequence
T-cell receptor
Infant
medicine.disease
Lymphoproliferative Disorders
TCR repertoire
Autoimmune lymphoproliferative syndrome
Autoimmune lymphoproliferative syndrome (ALPS)
CD8
030215 immunology
Zdroj: Journal of Immunology
Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2008, 181 (1), pp.440-8. ⟨10.4049/jimmunol.181.1.440⟩
Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2008, 181 (1), pp.440-8
Journal of Immunology, 2008, 181 (1), pp.440-8. ⟨10.4049/jimmunol.181.1.440⟩
ISSN: 1550-6606
0022-1767
Popis: The peripheral expansion of α/β+-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 TCRVβ 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 Vβ gene families that are used by their SP counterparts, though they dominantly use some Vβ 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 Vβ families. CDR3 sequencing of matching clonotypes revealed a significant sharing of CDR3 sequences from selected Vβ-Jβ transcripts between DN and CD8+ T cells. Altogether, these data strongly argue for a CD8 origin of DN T cells in ALPS.
Databáze: OpenAIRE
Externí odkaz: