At the heart of the study is the use of human precision-cut lung slices (PCLS). This ex vivo model enables the investigation of T-cell–mediated immune responses in human lung tissue while preserving the native tissue architecture. PCLS are generated from resected tissue and remain viable for several days. As a result, both the complex spatial organization of the lung parenchyma and the local immunological microenvironment are maintained.

Using multiparametric flow cytometry, cytokine analyses, and targeted immunological stimulation, the authors analyzed the composition, activatability, and functional plasticity of T-cell subpopulations within lung tissue. They found that a substantial proportion of CD8⁺ T cells in PCLS exhibit the phenotype of tissue-resident memory T cells (T_RM). These cells are characterized by high expression of the residency markers CD69 and CD103 and play a central role in local immune responses in the lung—for example during infections, chronic inflammatory diseases, or following immune interventions. At the same time, they are particularly sensitive to their immediate tissue environment. “Our aim was to understand how T cells are actually activated in human lung tissue and which factors influence their tissue residency,” explains Dr. Tonia Bargmann, first author of the study and researcher at BREATH at Fraunhofer ITEM. “PCLS allow us to investigate these processes in the native tissue context, thereby capturing aspects that cannot be addressed in classical cell culture systems.”

The results demonstrate that PCLS not only reliably reflect the presence of tissue-resident T cells in human lung tissue, but also realistically mirror their functional regulation under controlled stimulation conditions. Distinct activation and response patterns reveal that key immunological processes—such as T-cell activation, cytokine release, and tissue anchoring—can be studied in a context-dependent and reproducible manner in ex vivo tissue. In particular, the targeted modulation of CD103 expression under defined conditions points to a high degree of biological integrity and functional stability of the model. Thus, the study provides the first systematic functional evidence of tissue-resident T-cell responses in human lung tissue while preserving native tissue architecture.

PCLS are therefore suitable not only for descriptive analysis of immune cell populations, but also as a valid preclinical platform for the comparative investigation of immunological interventions. “PCLS allow us to analyze complex immune reactions in human lung tissue under physiologically relevant conditions and to address preclinical questions much closer to clinical reality,” says Dr. Armin Braun, senior author of the study and researcher at the DZL site BREATH. “Especially for studying immunomodulatory strategies and evaluating new therapeutic approaches, this model offers decisive added value over classical cell culture systems and animal models.”
 

Original publication:

Bargmann T, Sommer C, Stowasser L, Jacob S, Jürgen L, Konzok S, Werlein C, Zardo P, Neubert L, Jonigk D, Fieguth HG, Dahlmann F, Sewald K, Dehmel S, Braun A. 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.

Text: BREATH/ AB

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