title: The molecular and functional characterization of clonally expanded CD8+ TCR BV T cells in eosinophilic granulomatosis with polyangiitis (EGPA).
abstract: In eosinophilic granulomatosis with polyangiitis (EGPA) clonally expanded T cells might concur in granuloma formation and vascular injury. The TCR β-variable (BV) chain repertoire and third complementarity determining region (CDR3) of peripheral CD4+ and CD8+ cells in EGPA patients and age-matched controls and the expression of cytokines and chemokine receptors were investigated. The CD8+ lymphocytes of EGPA patients showed an increased frequency of BV expansions with a skewed profile of BV CDR3 lengths, increased CCR5 and CXCR3 expression and increased INFγ and TNFα production. In two patients, the TCR CDR3 cDNA sequences of the expanded BV family were identified. The CD4+ lymphocytes of EGPA patients revealed a higher expression of CRTH2 and increased production of IL-5. In conclusion, CD4+ T cells display a Th2 profile and CD8+ T cells are clonally expanded in EGPA and have a proinflammatory phenotype, suggesting their pathogenic role in vasculitic damage.
authors.affiliation: Allergology and Clinical Immunology, University of Torino, Italy; Medical Science Department, University of Torino, Italy. Electronic address: monica.boita@libero.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Boita
authors.affiliation: Internal Medicine II - Birago di Vische Hospital - ASL TO2, Torino, Italy. Electronic address: giuseppe.alesgui@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Guida
authors.affiliation: University Division of Hematology and Cell Therapy, AO Mauriziano, Torino, University of Torino, Italy; Molecular Biotechnology Center (MBC), University of Torino, Italy. Electronic address: paola.circosta@unito.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Circosta
authors.affiliation: University Division of Hematology and Cell Therapy, AO Mauriziano, Torino, University of Torino, Italy; Molecular Biotechnology Center (MBC), University of Torino, Italy. Electronic address: angelarita.elia@unito.it.
authors.forename: Angela Rita
authors.initials: AR
authors.lastname: Elia
authors.affiliation: Immunohematology and Transfusional Medicine - Giovanni Bosco Hospital - ASL TO2-Torino, Italy. Electronic address: stefania.stella@aslto2.piemonte.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Stella
authors.affiliation: Allergology and Clinical Immunology, University of Torino, Italy; Medical Science Department, University of Torino, Italy. Electronic address: enrico_heffler@yahoo.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Heffler
authors.affiliation: Allergology and Clinical Immunology, University of Torino, Italy. Electronic address: iuliana.badiu@gmail.com.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Badiu
authors.affiliation: Molecular Genetics Unit, University Hospital of Parma, Italy. Electronic address: dmartorana@ao.pr.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.affiliation: Medical Science Department, University of Torino, Italy. Electronic address: sara.mariani@unito.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Mariani
authors.affiliation: Allergology and Clinical Immunology, University of Torino, Italy; Medical Science Department, University of Torino, Italy. Electronic address: grolla@mauriziano.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rolla
authors.affiliation: University Division of Hematology and Cell Therapy, AO Mauriziano, Torino, University of Torino, Italy; Molecular Biotechnology Center (MBC), University of Torino, Italy. Electronic address: acignetti@mauriziano.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cignetti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015267:Churg-Strauss Syndrome / Q000097:blood / Q000276:immunology*; D022801:Complementarity Determining Regions; D005260:Female; D006099:Granuloma / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D019713:Receptors, CCR5 / Q000096:biosynthesis; D054367:Receptors, CXCR3 / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis; D011982:Receptors, Prostaglandin / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; C584933:CCR5 protein, human; C515187:CXCR3 protein, human; D022801:Complementarity Determining Regions; D015848:Interleukin-5; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C036293:prostaglandin D2 receptor
keywords: CD8+ lymphocytes; EGPA; Proinflammatory cytokines; TCR BV; Vasculitis