Article
Increased expression of the costimulatory c-type lectin (CD161) on circulating PR3-specific CD8+ and CD4+CD8+ T-cells in GPA
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Published: | February 5, 2019 |
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Background: Alterations of the peripheral T-cell compartment have been reported in granulomatosis with polyangiitis (GPA) such as the expansion of circulating CD4+CD8+ double-positive, CD4+CD161+ and CD28- effector memory T-cells (TEM) within the total CD3+ T-cell population. PR3-specific T-cells display Th2-type, Th17 and Th22 cytokine profiles in GPA. Moreover, concomitant cellular CMV- and Epstein Barr virus (EBV)-infection has been found to be associated with the expansion of CD28- TEM in GPA. However, expression of the C-type lectin CD161 on CD8+ and CD4+CD8+ double-positive proteinase 3 (PR3)-specific T-cells compared to other antigen-specific T-cells has not been described in GPA as yet.
Methods: This study analyzed the expression of CD161 and CD28 on antigen-specific CD3+CD8+ and CD3+CD4/CD8 double positive T cells in HLA-A2 positive patients with GPA (n=21) using flowcytometry. Antigen-specific T cells were detected using peptide / MHC class 1 dextramers containing peptide epitopes for PR3 (aa 196-177), Epstein Barr virus BMLF1 (EBV, aa 280-288) and Cytomegalovirus pp65 (CMV, aa 495-504).
Results: There was an increased expression of CD161 on both PR3-specific CD8+ and CD4+CD8+double-positive T-cells compared to EBV- or CMV-specific T-cells. The percentage of CD28+ T-cells was increased on PR3-specific CD8+ T-cells compared with EBV- and CMV-specific cells. CD28+ and CD28- PR3-specific CD8+ T-cells displayed an increased co-expression of CD161 compared to EBV-specific T-cells.
Conclusion: These findings suggest a possible role for CD161 as an additional TCR-independent co-stimulatory receptor on PR3-specific T-cells in GPA. The role of these cells in the pathophysiology and as a potential therapeutic target remains be further investigated.