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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.

Original publication

DOI

10.1016/j.clim.2007.12.004

Type

Journal article

Journal

Clin Immunol

Publication Date

05/2008

Volume

127

Pages

144 - 150

Keywords

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