T cells of patients with systemic sclerosis or Sjögren's disease display an aberrant metabolic state and memory phenotype in blood and lungs

Abstract

Objectives: Systemic sclerosis (SSc) and Sjögren's disease (SjD) are characterized by systemic inflammation. Although for both entities lymphocyte involvement is reported, the contribution of T-cell responses to lung manifestation of SSc and SjD remains elusive. Therefore, we aimed for systematically investigating T-cell responses in blood and lungs of patients with SSc or with SjD.

Methods: For deep T-cell characterization, blood and bronchoalveolar lavages (BALs) from patients with SSc (n = 38) or SjD (n = 36) and healthy controls (HC) (n = 34) were analyzed by spectral flow cytometry.

Results: Recirculating blood T cells of patients with SSc showed a significantly increased CD4+ terminally differentiated effector memory (TEMRA) compartment (P = 0.0171) and impaired mitochondrial fitness. In patients with SjD, blood CD8+ T cells were overall reduced and showed an increased expression of CD25 on memory subsets. CD8+ T cells in BAL of patients with SSc- or SjD-associated interstitial lung disease (ILD) expressed significant levels of CD69 and PD1, displaying an exhausted phenotype. In addition, conventional dendritic cells type 2 are highly activated and express increased levels of HLA-DR in BALs of patients with ILD.

Conclusion: In patients with SSc-ILD and SjD-ILD, a disturbed T-cell memory differentiation combined with an exhausted phenotype and reduced metabolic fitness point towards sustained T-cell receptor engagement and chronic stimulation. Thus, the retrieved data indicate a significant involvement of T cells in the disease pathology of SSc- and SjD-associated ILD.

Keywords: Sjögren’s disease; T cells; T-cell exhaustion; dendritic cells type 2; immunomodulation; interstitial lung disease; mitochondrial fitness; systemic autoimmune rheumatic disease; systemic sclerosis; terminally differentiated effector memory.