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

Abstract

Expansion of circulating CD28- T-cells reminiscent of effector memory T-cells (T(EM)) has been reported in Wegener's granulomatosis (WG) recently. To investigate the role of T(EM) in WG, we analyzed the expression of the activating NK-receptor NKG2D and its ligand MIC on circulating T(EM) and in granulomatous lesions, respectively. NKG2D was anomalously expressed and preferentially detected on circulating CD4+CD28- T(EM) in WG. Compared to healthy controls, T(EM) 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 T(EM) differentiation and proliferation--was also expressed in WG-granulomata. Thus, through acquisition of NK-like "innate" properties, IL-15 stimulated NKG2D+ T(EM) could interact with MIC+ cells within WG-granulomata, thereby sustaining inflammation and autoimmunity and promoting self-perpetuating pathology in WG.

• Authors: 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
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 127 Issue 2 Pg. 144-50 (May 2008) ISSN: 1521-7035 [Electronic] United States
• PMID: 18313361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD28 Antigens
• GPI-Linked Proteins
• Intercellular Signaling Peptides and Proteins
• Interleukin-15
• KLRK1 protein, human
• NK Cell Lectin-Like Receptor Subfamily K
• Receptors, Immunologic
• Receptors, Natural Killer Cell
• ULBP2 protein, human
• Myeloblastin

Topics

• Biopsy
• CD28 Antigens (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Flow Cytometry
• GPI-Linked Proteins
• Granulomatosis with Polyangiitis (blood, immunology)
• Humans
• Immunohistochemistry
• Immunologic Memory (immunology)
• Intercellular Signaling Peptides and Proteins (biosynthesis, immunology)
• Interleukin-15 (biosynthesis, immunology)
• Myeloblastin (immunology)
• NK Cell Lectin-Like Receptor Subfamily K
• Receptors, Immunologic (biosynthesis, blood, immunology)
• Receptors, Natural Killer Cell