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

Publication Type:

Journal Article


Clinical immunology (Orlando, Fla.), Volume 127, Issue 2, p.144-50 (2008)


2008, Antigens, CD28, Biopsy, CD4-Positive T-Lymphocytes, Center-Authored Paper, Clinical Research Division, Flow Cytometry Core Facility, GPI-Linked Proteins, 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, Shared Resources, Wegener Granulomatosis


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.