Expansion of circulating NKG2D+ effector memory T-cells and expression of NKG2D-ligand MIC in granulomaous lesions in Wegener's granulomatosis

Dorin Capraru, Antje Müller, Elena Csernok, Wolfgang L. Gross, Konstanze Holl-Ulrich, John Northfield, Paul Klenerman, Karen Herlyn, Julia Holle, Stefan Gottschlich, Jan Voswinkel, Thomas Spies, Ursula Fagin, Wolfram J. Jabs, Peter Lamprecht*

*Corresponding author for this work
56 Citations (Scopus)

Abstract

Expansion of circulating CD28- T-cells reminiscent of effector memory T-cells (TEM) has been reported in Wegener's granulomatosis (WG) recently. To investigate the role of TEM in WG, we analyzed the expression of the activating NK-receptor NKG2D and its ligand MIC on circulating TEM and in granulomatous lesions, respectively. NKG2D was anomalously expressed and preferentially detected on circulating CD4+CD28- TEM in WG. Compared to healthy controls, TEM display a more activated phenotype potentially favoring unbalanced proinflammatory responses in WG. Cluster-like formations of "Wegener's autoantigen" PR3 were surrounded by NKG2D+ and NKG2D-ligand MIC+ cells in WG-granulomata, but not in disease controls. Further, IL-15 - known to drive TEM differentiation and proliferation - was also expressed in WG-granulomata. Thus, through acquisition of NK-like "innate" properties, IL-15 stimulated NKG2D+ TEM could interact with MIC+ cells within WG-granulomata, thereby sustaining inflammation and autoimmunity and promoting self-perpetuating pathology in WG.

Original languageEnglish
JournalClinical Immunology
Volume127
Issue number2
Pages (from-to)144-150
Number of pages7
ISSN1521-6616
DOIs
Publication statusPublished - 05.2008

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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