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

doi:10.1016/j.clim.2007.12.004

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

64 Citations (Scopus)

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.

Original language	English
Journal	Clinical Immunology
Volume	127
Issue number	2
Pages (from-to)	144-150
Number of pages	7
ISSN	1521-6616
DOIs	https://doi.org/10.1016/j.clim.2007.12.004
Publication status	Published - 05.2008

Funding

Supported by KFO170 (AM, EC, WLG, JH, PL) from the German Research Society (Deutsche Forschungsgemeinschaft/DFG), and grants from the Vasculitis foundation Kansas City USA (AM, EC, WLG, PL), Innovationsfonds Schleswig-Holstein (PL), Verein zur Förderung der Erforschung und Bekämpfung rheumatischer Erkrankungen Bad Bramstedt e.V., Germany (AM, EC, WLG, PL), and Wellcome trust (PK).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

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

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Capraru, D., Müller, A., Csernok, E., Gross, W. L., Holl-Ulrich, K., Northfield, J., Klenerman, P., Herlyn, K., Holle, J., Gottschlich, S., Voswinkel, J., Spies, T., Fagin, U., Jabs, W. J., & Lamprecht, P. (2008). Expansion of circulating NKG2D+ effector memory T-cells and expression of NKG2D-ligand MIC in granulomaous lesions in Wegener's granulomatosis. Clinical Immunology, 127(2), 144-150. https://doi.org/10.1016/j.clim.2007.12.004

@article{e8ec8f9dacf048b88d3c11e9627dcd69,

title = "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 (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.",

author = "Dorin Capraru and Antje M{\"u}ller and Elena Csernok and Gross, \{Wolfgang L.\} and Konstanze Holl-Ulrich and John Northfield and Paul Klenerman and Karen Herlyn and Julia Holle and Stefan Gottschlich and Jan Voswinkel and Thomas Spies and Ursula Fagin and Jabs, \{Wolfram J.\} and Peter Lamprecht",

note = "Funding Information: Supported by KFO170 (AM, EC, WLG, JH, PL) from the German Research Society (Deutsche Forschungsgemeinschaft/DFG), and grants from the Vasculitis foundation Kansas City USA (AM, EC, WLG, PL), Innovationsfonds Schleswig-Holstein (PL), Verein zur F{\"o}rderung der Erforschung und Bek{\"a}mpfung rheumatischer Erkrankungen Bad Bramstedt e.V., Germany (AM, EC, WLG, PL), and Wellcome trust (PK). Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2008",

month = may,

doi = "10.1016/j.clim.2007.12.004",

language = "English",

volume = "127",

pages = "144--150",

journal = "Clinical Immunology",

issn = "1521-6616",

publisher = "Academic Press Inc.",

number = "2",

}

Capraru, D, Müller, A, Csernok, E, Gross, WL, Holl-Ulrich, K, Northfield, J, Klenerman, P, Herlyn, K, Holle, J, Gottschlich, S, Voswinkel, J, Spies, T, Fagin, U, Jabs, WJ & Lamprecht, P 2008, 'Expansion of circulating NKG2D+ effector memory T-cells and expression of NKG2D-ligand MIC in granulomaous lesions in Wegener's granulomatosis', Clinical Immunology, vol. 127, no. 2, pp. 144-150. https://doi.org/10.1016/j.clim.2007.12.004

TY - JOUR

T1 - Expansion of circulating NKG2D+ effector memory T-cells and expression of NKG2D-ligand MIC in granulomaous lesions in Wegener's granulomatosis

AU - Capraru, Dorin

AU - Müller, Antje

AU - Csernok, Elena

AU - Gross, Wolfgang L.

AU - Holl-Ulrich, Konstanze

AU - Northfield, John

AU - Klenerman, Paul

AU - Herlyn, Karen

AU - Holle, Julia

AU - Gottschlich, Stefan

AU - Voswinkel, Jan

AU - Spies, Thomas

AU - Fagin, Ursula

AU - Jabs, Wolfram J.

AU - Lamprecht, Peter

N1 - Funding Information: Supported by KFO170 (AM, EC, WLG, JH, PL) from the German Research Society (Deutsche Forschungsgemeinschaft/DFG), and grants from the Vasculitis foundation Kansas City USA (AM, EC, WLG, PL), Innovationsfonds Schleswig-Holstein (PL), Verein zur Förderung der Erforschung und Bekämpfung rheumatischer Erkrankungen Bad Bramstedt e.V., Germany (AM, EC, WLG, PL), and Wellcome trust (PK). Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2008/5

Y1 - 2008/5

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/41749091572

U2 - 10.1016/j.clim.2007.12.004

DO - 10.1016/j.clim.2007.12.004

M3 - Journal articles

C2 - 18313361

AN - SCOPUS:41749091572

SN - 1521-6616

VL - 127

SP - 144

EP - 150

JO - Clinical Immunology

JF - Clinical Immunology

IS - 2

ER -

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

Abstract

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