Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus.
BACKGROUND
There is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL-17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134.


METHODS
Thirty-four patients (3 male, 31 female, mean age 41 ± 15 years) fulfilling at least four of the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE and 24 healthy controls were enrolled. T-cells from the peripheral blood were analysed by fluorescence activated cell sorting (FACS) for their expression levels of CD80, CD134 and CCR6. In vitro stimulated CD3+IL17+ cells were also investigated for the expression of these costimulatory markers. Finally, renal biopsies from SLE patients were evaluated for the presence of CD134 expressing T-cells.


RESULTS
Percentages of IL-17 expressing T-cells were significantly increased in patients with active disease as compared to healthy controls (1.46 ± 0.58% versus 0.93 ± 0.30%, P = 0.007). The percentage of IL-17 producing T-cells was correlated with disease activity as assessed by systemic lupus erythematosus disease activity index (SLEDAI) (r = 0.53, P = 0.003). In patients, most of the IL-17 producing T-cells were confined to the CCR6+ T-cell subset (80 ± 13%). Expression of CD80 and CD134 on the IL-17 producing T-cell subset was higher in SLE than in healthy controls (HC) (CD134: 71.78 ± 14.51% versus 51.45 ± 16.58%, P = 0.002; CD80: 25.5 ± 14.99% versus 14.99 ± 5.74%, P = 0.02). Also, patients with lupus nephritis expressed higher levels of CD134+ on CD3+IL-17+ cells as compared to HC (72.69 ± 11.54% versus 51.45 ± 16.58%, P = 0.006). Furthermore, renal biopsies of lupus nephritis patients showed infiltration of CD134+ T cells.


CONCLUSIONS
Percentages of IL-17 expressing T-cells correlate with disease activity. Further, these cells show increased expression of costimulatory markers such as CD134 and CD80. The presence of CD134+ T-cells in renal biopsies of lupus nephritis patients suggest that these cells migrate to the kidney and might contribute to inflammatory processes through IL-17 secretion.
Dolff
Sebastian
S
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, Essen, Germany. Sebastian.Dolff@uk-essen.de
Quandt
Daniel
D
Wilde
Benjamin
B
Feldkamp
Thorsten
T
Hua
Fan
F
Cai
Xin
X
Specker
Christof
C
Kribben
Andreas
A
Kallenberg
Cees G M
CG
Witzke
Oliver
O
D000328:Adult; D018122:B7-1 Antigen / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000378:metabolism; D053262:Receptors, OX40 / Q000378:metabolism*; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000378:metabolism* / Q000473:pathology
D018122:B7-1 Antigen; D015415:Biomarkers; C106311:CCR6 protein, human; D020381:Interleukin-17; D054399:Receptors, CCR6; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human