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^*

^*Korrespondierende/r Autor/-in für diese Arbeit

64 Zitate (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.

Originalsprache	Englisch
Zeitschrift	Clinical Immunology
Jahrgang	127
Ausgabenummer	2
Seiten (von - bis)	144-150
Seitenumfang	7
ISSN	1521-6616
DOIs	https://doi.org/10.1016/j.clim.2007.12.004
Publikationsstatus	Veröffentlicht - 05.2008

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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).

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SDG 3 – Gesundheit und Wohlergehen

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Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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10.1016/j.clim.2007.12.004

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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, Jg. 127, Nr. 2, S. 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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