Differences in CCR5 expression on peripheral blood CD4+CD28- T-cells and in granulomatous lesions between localized and generalized Wegener's granulomatosis.
Wegener's granulomatosis (WG) is an autoimmune disease characterized by granulomatous lesions and a necrotizing vasculitis. Th1-type-cells lacking CD28 are expanded independent of age and immunosuppressive therapy in WG. To address their migratory properties of CD4(+)CD28(-) T-cells we studied the expression of the inducible inflammatory Th1-type chemokine receptor CCR5 in localized WG and generalized WG. Expansion of CD4(+)CD28(-) T-cells was more prominent in generalized WG compared to localized WG. In localized WG a larger fraction of CD4(+)CD28(-) T-cells displayed CCR5 expression compared to generalized WG. CCR5 expression was also higher in granulomatous lesions in localized WG. Higher levels of CCR5 expression on CD4(+)CD28(-) T-cells in localized WG may favor stronger CCR5-mediated recruitment of this T-cell subset into granulomatous lesions in localized WG. Expansion of Th-1-type CD4(+)CD28(-)CCR5(+) effector memory T-cells might contribute to disease progression and autoreactivity, either directly, by maintaining the inflammatory response, or as a result of bystander activation.
Lamprecht
Peter
P
Department of Rheumatology, University Hospital of Schleswig-Holstein, Campus Luebeck, and Rheumaklinik Bad Bramstedt, Ratzeburger Allee 160, 23538 Luebeck, Germany. lamprecht@rheuma-zentrum.de
Bruhl
Hilke
H
Erdmann
Anika
A
Holl-Ulrich
Konstanze
K
Csernok
Elena
E
Seitzer
Ulrike
U
Mack
Matthias
M
Feller
Alfred C
AC
Reinhold-Keller
Eva
E
Gross
Wolfgang L
WL
Muller
Antje
A
D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D014890:Granulomatosis with Polyangiitis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics
D018106:CD28 Antigens; D019713:Receptors, CCR5