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

Abstract

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. 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. 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. 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.