[Effector memory Tcells in the pathogenesis of ANCA-associated vasculitides. German version]. / Effektor-Memory-TZellen in der Pathogenese von ANCA-assoziierten Vaskulitiden.
Z Rheumatol
; 75(2): 183-6, 2016 Mar.
Article
em De
| MEDLINE
| ID: mdl-26913718
ABSTRACT
Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) have an expansion of effector memory Tcells in peripheral blood. The enlarged effector memory cell population contains distinct cell subsets, including Thelper type 1 (Th1) CD4+ Tcells lacking co-stimulatory CD28 expression and Th17 cells in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and Th2 type and Th17 cells in eosinophilic granulomatosis with polyangiitis (EGPA). The cytokine response of autoreactive proteinase 3 (PR3)-specific effector memory Tcells is skewed towards an increase of Th2 type, Th17 and Th22 cell fractions in GPA. Anomalous effector memory CD4+ Tcell co-stimulation is suggested by the aberrant expression of Pselectin glycoprotein ligand1, beta2 integrin, chemokine receptors, natural-killer group 2 member D (NKG2D) and other activating receptors. The increased expression of these receptors is accompanied by Tcell activation and migration to inflamed tissues. The Tcells are abundant and secrete proinflammatory cytokines in inflammatory lesions in AAV. The Tcell mediated tissue damage correlates with renal outcome, whereas B-cell infiltration does not. Activation of lesional CD4+NKG2D+ effector memory Tcells is independent of the antigen; moreover, CD4+NKG2D+ effector memory Tcells display NK-cell-like cytotoxicity towards microvascular endothelial cells in vitro. Thus, effector memory Tcells play an important role in tissue damage and disease progression in AAV. Sequentially administered or combined with B-cell depleting therapy, Tcell-directed therapies, especially those directed against effector memory CD4+ Tcells, may further improve the outcome and help to achieve long-term remission in AAV.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Auxiliares-Indutores
/
Modelos Imunológicos
/
Anticorpos Anticitoplasma de Neutrófilos
/
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos
/
Imunoterapia
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
De
Revista:
Z Rheumatol
Ano de publicação:
2016
Tipo de documento:
Article