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Clin Immunol. 2014 May-Jun;152(1-2):152-63. doi: 10.1016/j.clim.2014.03.001. Epub 2014 Mar 13.

The molecular and functional characterization of clonally expanded CD8+ TCR BV T cells in eosinophilic granulomatosis with polyangiitis (EGPA).

Author information

1
Allergology and Clinical Immunology, University of Torino, Italy; Medical Science Department, University of Torino, Italy. Electronic address: monica.boita@libero.it.
2
Internal Medicine II - Birago di Vische Hospital - ASL TO2, Torino, Italy. Electronic address: giuseppe.alesgui@gmail.com.
3
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.
4
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.
5
Immunohematology and Transfusional Medicine - Giovanni Bosco Hospital - ASL TO2-Torino, Italy. Electronic address: stefania.stella@aslto2.piemonte.it.
6
Allergology and Clinical Immunology, University of Torino, Italy; Medical Science Department, University of Torino, Italy. Electronic address: enrico_heffler@yahoo.it.
7
Allergology and Clinical Immunology, University of Torino, Italy. Electronic address: iuliana.badiu@gmail.com.
8
Molecular Genetics Unit, University Hospital of Parma, Italy. Electronic address: dmartorana@ao.pr.it.
9
Medical Science Department, University of Torino, Italy. Electronic address: sara.mariani@unito.it.
10
Allergology and Clinical Immunology, University of Torino, Italy; Medical Science Department, University of Torino, Italy. Electronic address: grolla@mauriziano.it.
11
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.

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.

KEYWORDS:

CD8+ lymphocytes; EGPA; Proinflammatory cytokines; TCR BV; Vasculitis

PMID:
24632064
DOI:
10.1016/j.clim.2014.03.001
[Indexed for MEDLINE]
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