Peripheral blood responses to specific antigens and CD28 in sarcoidosis

Abstract

Background: Potential antigens inducing sarcoid inflammation include mycobacterial and auto-antigens. Paradoxically, peripheral anergy to common recall antigens also occurs, possibly due to impaired dendritic cell or regulatory T-cell responses, or impaired T-cell co-stimulation. The purpose of this study was to compare peripheral blood responses of patients with sarcoidosis to candidate antigens, and examine CD28 T-cell co-stimulation.

Methods: Peripheral blood mononuclear cell (PBMC) responses were examined from patients with sarcoidosis (n=16) and healthy control subjects (n=22) following PBMC stimulation with: anti-CD3/CD28 coated beads; Mycobacterium tuberculosis ESAT-6 and KatG peptides; vimentin and lysyl tRNA peptides; and common recall antigens, including cytomegalovirus (CMV) cell lysate as well as CMV, Epstein-Barr virus, influenza virus (CEF) peptides.

Results: ESAT-6/KatG peptide stimulation induced greater numbers of IFN-γ producing T-cells, and elevated IL-2, IL-6 and TNF-α production in sarcoidosis compared to purified protein derivative (PPD)-negative healthy control subjects. PBMCs from patients with sarcoidosis showed reduced IFN-γ producing T-cells following stimulation with CMV lysate, CEF peptides and CD3/CD28 beads; and reduced IL-4 and TNF-α production following CD3/CD28 activation.

Conclusions: Patients with sarcoidosis exhibit greater PBMC responses to M. tuberculosis antigens compared to PPD-negative controls, but reduced T-cell responses to common recall antigens. One contributing mechanism may be impairment of T-cell CD28 co-stimulation.