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Background <p>Resident immune cells are central in shaping the lung’s tissue-specific immunity. Precision-cut lung slices (PCLS) preserve the native tissue microenvironment and are therefore an excellent ex vivo model to analyze residency and functionality of resident memory T cells.</p> Methods <p>To study the modulation of tissue residency markers and T cell activation in the native lung niche, we treated PCLS with broad and T cell-specific stimuli and analyzed responses using flow cytometry and mediator secretion analysis. Using TGFβ, anti-CD3/CD28, IL-2 and a pool of MHC-I restricted peptides we analyzed cytokine secretion, CD4<sup>+</sup>/CD8<sup>+</sup> T cell ratios, and the expression of activation and residency markers.</p> Results <p>First, we characterized lung immune cell in PCLS which also revealed that resident memory T cells are abundant in PCLS. We showed that regulation of the tissue residency marker CD103 is dependent on TGFβ or IL-2 signaling in combination with T cell receptor engagement. Further, polyclonal activation of T cells in the tissue reduced tissue secretion of anti-inflammatory cytokines like TGFβ, while increasing the secretion of T cell-associated cytokines like IFNγ, IL-2, and Granzyme B. This shift was supported by an upregulation of T cell activation markers such as CD39, CD137, and Ki-67. Finally, treatment of PCLS with a pool of MHC-I-restricted peptides led to increased secretion of multiple inflammatory effector cytokines associated and a specific activation of tissue resident T cells.</p> Conclusion <p>Taken together, we have demonstrated that PCLS provide an excellent platform to modulate tissue resident T cell responses influenced by human lung tissue microenvironment.</p>

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Regulation of T cell tissue residency and activation in human PCLS

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月15日

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  • Tonia Bargmann,
  • Charline Sommer,
  • Lena Stowasser,
  • Sophie Jacob,
  • Louisa Jürgen,
  • Sebastian Konzok,
  • Christopher Werlein,
  • Patrick Zardo,
  • Lavinia Neubert,
  • Danny Jonigk,
  • Hans-Gerd Fieguth,
  • Franziska Dahlmann,
  • Katherina Sewald,
  • Susann Dehmel,
  • Armin Braun

摘要

Background

Resident immune cells are central in shaping the lung’s tissue-specific immunity. Precision-cut lung slices (PCLS) preserve the native tissue microenvironment and are therefore an excellent ex vivo model to analyze residency and functionality of resident memory T cells.

Methods

To study the modulation of tissue residency markers and T cell activation in the native lung niche, we treated PCLS with broad and T cell-specific stimuli and analyzed responses using flow cytometry and mediator secretion analysis. Using TGFβ, anti-CD3/CD28, IL-2 and a pool of MHC-I restricted peptides we analyzed cytokine secretion, CD4+/CD8+ T cell ratios, and the expression of activation and residency markers.

Results

First, we characterized lung immune cell in PCLS which also revealed that resident memory T cells are abundant in PCLS. We showed that regulation of the tissue residency marker CD103 is dependent on TGFβ or IL-2 signaling in combination with T cell receptor engagement. Further, polyclonal activation of T cells in the tissue reduced tissue secretion of anti-inflammatory cytokines like TGFβ, while increasing the secretion of T cell-associated cytokines like IFNγ, IL-2, and Granzyme B. This shift was supported by an upregulation of T cell activation markers such as CD39, CD137, and Ki-67. Finally, treatment of PCLS with a pool of MHC-I-restricted peptides led to increased secretion of multiple inflammatory effector cytokines associated and a specific activation of tissue resident T cells.

Conclusion

Taken together, we have demonstrated that PCLS provide an excellent platform to modulate tissue resident T cell responses influenced by human lung tissue microenvironment.