Session Information
Session Title: T cell Biology and Targets in Autoimmune Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose
Previous studies have demonstrated the implication of CD4+ T cells, especially T helper (Th1) and Th17 cells, in the pathogenesis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). However, very little is known concerning CD8+ T cells. This study aimed to investigate their implication in the pathogenesis of GCA and PMR.
Methods
Thirty patients suffering from GCA (n=23) or PMR (n=7) and 21 age-matched healthy volunteers were enrolled. Blood samples were collected at diagnosis and after 3 months of glucocorticoid (GC) treatment. Percentages of circulating cytotoxic T lymphocytes (CTL) (CD3+CD8+Perforine+GranzymeB+), Tc1 cells (CD3+CD8+IFN-γ+), Tc17 cells (CD3+CD8+IL-17+) and the expression of CD63, HLA-DR, CCR5, CCR6, CCR7, CD62L and CXCR3 by CD8+ T lymphocytes were assessed by flow cytometry analysis. Levels of soluble Granzyme A, Granzyme B, CCL2, CCL20, CXCL9, CXCL10 and CXCL11 were determined by ELISA or Luminex® technology. Temporal artery biopsies (TAB) were stained for CD3, CD4 and CD8. Data are expressed by mean±SEM and P value is the result of the Mann Whitney U test or Wilcoxon matched-pairs signed rank test, when appropriate.
Results
Percentages of circulating CTL and Tc17 in total CD8+ T cells were significantly increased in patients compared to controls: 36.6±4.1 vs. 16.3±3.1% (P=0.0004) and 0.59±0.11 vs. 0.15±0.03% (P<0.0001), respectively. The level of Tc1 cells was not different between two groups. CD63 expression, that is expressed at the membrane once CTL have degranulated, was higher in patients than in controls (29.3±3.5 vs. 14.8±2.9%; P=0.003). Levels of Granzyme A and B were also significantly increased in the serum of patients when compared to controls: 20.6±4.4 vs. 11.6±2.7 pg/mL (P=0.02) and 3.2±1.3 vs. 0.95±0.49 pg/mL (P=0.004), respectively. After 3 months of GC treatment, percentages of circulating CTL, Tc17 and soluble levels of Granzyme A and B were significantly decreased, whereas the percentages of Tc1 and CD63+cells in total CD8+ T lymphocytes remained stable. Expression of chemokine receptors was comparable between patients and controls except for CXCR3 that was expressed at a higher level by CD8+ T cells from patients: 48.1±3.6 vs. 28.5±3.5% (P=0.0004). Levels of CXCR3 ligands were increased in the serum of patients compared to controls: 629.8±194.7 vs. 92.81±19.2 pg/mL (P<0.0001) for CXCL9, 31.4±6.9 vs. 9.2±1.5 pg/mL (P<0.0001) for CXCL10 and 12.0±4.1 vs. 3.5±2.7 pg/mL (P=0.0094) for CXCL11. Importantly, the levels of these 3 chemokines were decreased after 3 months of GC treatment. Immunohistochemical analyses of TAB (5 GCA patients) revealed a strong infiltration by CD4+ and CD8+ T cells in all the layers of the artery.
Conclusion
This study provides the first data that demonstrate an implication of CD8+ T cells in the pathogenesis of GCA and PMR. In untreated patients, CD8+ T cells, that infiltrate lesions of vasculitis, have an activated phenotype that is partly corrected by GC treatment. CXCR3 is upregulated on CD8+ T cells from GCA and PMR patients while levels of CCL9, -10 and -11 are increased in the serum of patients, which argues for the implication of CXCR3 in the homing of CD8+ T cells in the lesions of GCA.
Disclosure:
M. Samson,
None;
S. Audia,
None;
M. Trad,
None;
M. Ciudad,
None;
H. Devilliers,
None;
A. Gautheron,
None;
V. Quipourt,
None;
F. Maurier,
None;
N. Meaux Ruault,
None;
P. Manckoundia,
None;
P. Ornetti,
None;
J. F. Maillefert,
None;
J. F. Besancenot,
None;
C. Ferrand,
None;
P. Saas,
None;
L. Martin,
None;
N. Janikashvili,
None;
B. Bonnotte,
None.
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