How T Cells Contribute to Autoimmune-Associated Lung Disease

An interdisciplinary study by DZL researchers at the BREATH site in Hannover investigates how certain immune cells, called T cells, contribute to changes in the lungs that occur in systemic autoimmune diseases. These changes, known as interstitial lung manifestations (ILD), can damage lung tissue and impair lung function. The results of the study were published in Rheumatology (Oxford) and provide new insights into how immune processes in the blood and lungs interact to drive these diseases.

The researchers analyzed blood samples and lung fluids, known as bronchoalveolar lavages (BAL), from patients with systemic sclerosis (SSc) or Sjögren’s syndrome (SjD), as well as from healthy control participants. Systemic sclerosis is an autoimmune disease that mainly affects the skin and internal organs, causing tissue thickening and hardening. Sjögren’s syndrome is an autoimmune disease in which the immune system attacks the saliva and tear glands, leading to dry mucous membranes and inflammation. Both diseases can also affect the lungs and cause inflammatory changes in lung tissue. The goal of the study was to identify changes in the behavior and metabolism of immune cells that contribute to lung damage.

The analyses revealed clear differences in T cells between the two diseases. In patients with systemic sclerosis, a specific type of T cell called TEMRA T cells (terminally differentiated memory CD4⁺ T cells) was significantly more frequent in the blood. These cells showed reduced energy production, meaning they are constantly active but no longer function properly – in other words, they are “exhausted.” In patients with Sjögren’s syndrome, there was a reduction in cytotoxic CD8⁺ T cells, while other memory T cells were more strongly activated, indicating that the immune system is chronically stimulated.

Examination of the BAL samples provided direct insights into immune processes within the lungs. In patients with SSc- or SjD-associated ILD, the researchers found an increased number of CD8⁺ T cells marked by CD69⁺ and PD-1⁺, a pattern indicative of chronically activated, exhausted cells, which likely contribute to persistent lung inflammation. In addition, there was enhanced activation of conventional dendritic cells type 2 (cDC2). These cells play a key role in stimulating T cells and maintaining the immune response within lung tissue.

The findings make it clear that lung changes in autoimmune diseases are not solely caused by direct tissue damage but are driven by complex immune system processes. Altered metabolism, signs of T cell exhaustion, and changes in T cell differentiation point to chronic immune activation, which may worsen disease progression.

“These data show how closely immune cell metabolism and function are linked – and that this connection has been largely underestimated in autoimmune-associated lung disease,” explains Dr. Theresa Graalmann, researcher at the Center for Experimental and Clinical Infection Research Twincore Hannover and the Clinic for Rheumatology and Immunology at Hannover Medical School, and last author of the publication.

Source: Interdisciplinary study investigates the role of T cells in autoimmune-associated lung diseases

Original publication: Ehlers C, Biermann H, Thiele T, et al. T cells of patients with systemic sclerosis or Sjögren's disease display an aberrant metabolic state and memory phenotype in blood and lungs. Rheumatology (Oxford). 2025;64(8):4806–4815. doi:10.1093/rheumatology/keaf198