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

Journal article

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: Capraru, D; Müller, A; Csernok, E; Gross, W; Holl-Ulrich, K

• Publication status: Published
• Journal: Clinical immunology (Orlando, Fla.)
• Volume: 127
• Issue: 2
• Pages: 144-150
• Publication date: 2008-05-01
• DOI: 10.1016/j.clim.2007.12.004
• EISSN: 1521-7035
• ISSN: 1521-6616
• Language: English
• Keywords: Humans; Immunohistochemistry; Wegener Granulomatosis; Biopsy; Myeloblastin; Receptors, Natural Killer Cell; Interleukin-15; GPI-Linked Proteins; NK Cell Lectin-Like Receptor Subfamily K; CD4-Positive T-Lymphocytes; Flow Cytometry; Receptors, Immunologic; Intercellular Signaling Peptides and Proteins; Antigens, CD28; Immunologic Memory