CD4+CD25+ T-cell populations expressing CD134 and GITR are associated with disease activity in patients with Wegener's granulomatosis.
BACKGROUND
An increased CD4(+) CD25(+) T-cell population is observed in Wegener's granulomatosis (WG). This T-cell population is not well characterized yet and their contribution to the disease pathogenesis remains obscure.


METHODS
Thirty patients with WG and 18 healthy controls (HC) were included in this study. The disease activity and extension were measured by the Birmingham Vasculitis Activity Score (BVAS) and the Disease Extent Index (DEI). Lymphocytes from peripheral blood were analysed by FACS for the expression of CD4, CD25, CD134 and GITR. Cytokine expression in these subsets was assessed too. Nasal, lung and renal tissues from WG patients were immunohistochemically stained for CD3 and CD134.


RESULTS
The percentage of CD134(+) as well as GITR(+) expressing CD4(+)CD25(+) lymphocytes was increased in patients as compared to HC (37 +/- 12% versus 27 +/- 8%, P = 0.005; 18 +/- 9% versus 11 +/- 6%, P = 0.003). The expression of CD134 and GITR showed a significant correlation with disease activity (r = 0.5, P = 0.009; r = 0.55, P = 0.001). Most of these displayed the phenotype of effector memory T-cells (94 +/- 4% and 91 +/- 6%). CD134 T-cells were found in tissues affected by WG.


CONCLUSIONS
CD4(+)CD25(+) effector memory T-cells expressing CD134 and GITR seem to play a role in disease mechanisms, as suggested by their close association with disease activity and their participation in inflammatory process.
Wilde
Benjamin
B
Department of Nephrology, University Duisburg-Essen, Essen, Germany.
Dolff
Sebastian
S
Cai
Xin
X
Specker
Christof
C
Becker
Jan
J
Tötsch
Martin
M
Costabel
Ulrich
U
Dürig
Jan
J
Kribben
Andreas
A
Tervaert
Jan Willem Cohen
JW
Schmid
Kurt Werner
KW
Witzke
Oliver
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D053450:Glucocorticoid-Induced TNFR-Related Protein; D014890:Granulomatosis with Polyangiitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D053262:Receptors, OX40 / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit; D017475:Receptors, Nerve Growth Factor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; C505716:TNFRSF4 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma