T cells are a central component of the adaptive immune system. They recognize pathogens, fight infections, and form immune memory. How these immune cells are activated in human lung tissue and which factors influence their residence in the tissue has long been difficult to observe directly. Researchers at the German Center for Lung Research (DZL) at the BREATH site have now used an innovative ex vivo model to make these processes visible: precision-cut lung slices (PCLS).
The focus of the study is on the use of human PCLS. This ex vivo model allows T cell–mediated immune responses to be studied in human lung tissue while preserving its native tissue architecture. PCLS are prepared from resected tissue and remain viable for several days, maintaining both the complex spatial organization of the lung parenchyma and the local immunological microenvironment.
Using modern laboratory techniques such as flow cytometry, analyses of immune signaling molecules (cytokines), and targeted stimulation, the authors investigated which T cells are present in the lung tissue, how responsive they are, and how flexible their functions are. They found that many of the CD8⁺ T cells in PCLS exhibit the characteristics of tissue-resident memory T cells (TRM). These cells carry important markers (CD69 and CD103) and play a key role in local immune responses in the lung, for example during infections, chronic inflammation, or after immunotherapies. At the same time, they are highly sensitive to changes in their immediate tissue environment.
“Our goal was to understand how T cells in human lung tissue are actually activated and which factors influence their tissue residency,” explains Dr. Tonia Bargmann, first author of the study and researcher at BREATH, Fraunhofer ITEM. “PCLS allow us to study these processes in the native tissue context and thus capture aspects that cannot be observed in conventional cell culture systems.”
The results show that PCLS not only reliably represent the presence of tissue-resident T cells but also realistically reflect their functional behavior under controlled conditions. Differences in activation and response demonstrate that central immune processes, such as T cell activation, cytokine release, and tissue anchoring, can be studied in a context-dependent and reproducible manner. The targeted modulation of CD103 expression under defined conditions further demonstrates the biological accuracy and stability of the model. This study provides the first systematic functional evidence of tissue-resident T cell responses in human lung tissue while preserving the natural tissue architecture.
PCLS are therefore not only suitable for descriptive analyses of immune cell populations but also serve as a valid preclinical platform for comparative studies of immunological interventions. “PCLS allow us to analyze complex immune responses in human lung tissue under physiologically relevant conditions and to address preclinical questions much closer to the clinical reality,” says Dr. Armin Braun, last author of the study and researcher at DZL-BREATH. “Especially for investigating immunomodulatory strategies and evaluating new therapeutic approaches, this model offers a significant advantage over conventional cell cultures and animal models.”
Original publication: Bargmann T, Sommer C, Stowasser L et al. Regulation of T cell tissue residency and activation in human PCLS. Respir Res. 2025 Nov 15;26(1):319. doi: 10.1186/s12931-025-03397-1. PMID: 41241731; PMCID: PMC12619209.
Source: BREATH
