Dataset Information

Antigen presentation by lung epithelial cells directs CD4⁺ T_RM cell function and regulates barrier immunity.

ABSTRACT: Barrier tissues are populated by functionally plastic CD4⁺ resident memory T (T_RM) cells. Whether the barrier epithelium regulates CD4⁺ T_RM cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)^lowMHC^high epithelial cells, function as anatomically-segregated and temporally-dynamic antigen presenting cells. In vivo ablation of lung epithelial MHC-II results in altered localization of CD4⁺ T_RM cells. Recurrent encounters with cognate antigen in the absence of epithelial MHC-II leads CD4⁺ T_RM cells to co-express several classically antagonistic lineage-defining transcription factors, changes their cytokine profiles, and results in dysregulated barrier immunity. In addition, lung epithelial MHC-II is needed for surface expression of PD-L1, which engages its ligand PD-1 to constrain lung CD4⁺ T_RM cell phenotypes. Thus, we establish epithelial antigen presentation as a critical regulator of CD4⁺ T_RM cell function and identify epithelial-CD4⁺ T_RM cell immune interactions as core elements of barrier immunity.

SUBMITTER: Shenoy AT

PROVIDER: S-EPMC8492657 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Human cytomegalovirus (HCMV) persistently infects 40-90% of the human population but in the face of a normal immune system, viral spread and dissemination are efficiently controlled thus preventing clinically signs and disease. HCMV-infected hosts produce a remarkably large amount of HCMV-specific CD4+ and CD8+ T cells that can even reach 20-50% of total T memory cells in the elderly. How HCMV may elicit such large and long-lasting T-cell responses in the absence of detectable viremia has not been elucidated yet. Additionally, HCMV is known to encode several gene products that potently inhibit T-cell recognition of infected cells. The best characterized are the four immune evasive US2, US3, US6, and US11 genes that by different mechanisms account for major histocompatibility complex (MHC) class I and class II degradation and intracellular retention in infected cells. By infecting M1 and M2 human macrophages (Mφ) with the wild-type HCMV strain TB40E or a mutant virus deleted of the four immune evasive genes US2, US3, US6, and US11, we demonstrated that human Mφ counteract the inhibitory potential of the US2-11 genes and remain capable to present peptides via MHC class I and class II molecules. Moreover, by sorting the infected and bystander cells, we provide evidence that both infected and bystander Mφ contribute to antigen presentation to CD4+ and CD8+ T cells. The T cells responding to TB40E-infected Mφ show markers of the T effector memory compartment, produce interferon-γ, and express the lytic granule marker CD107a on the cell surface, thus mirroring the HCMV-specific T cells present in healthy seropositive individuals. All together, our findings reveal that human Mφ escape inhibition of MHC-dependent antigen presentation by HCMV and continue to support T cell proliferation and activation after HCMV infection. Taking into account that Mφ are natural targets of HCMV infection and a site of viral reactivation from latency, our findings support the hypothesis that Mφ play crucial roles for the lifelong maintenance and expansion of HCMV-committed T cells in the human host.

Dataset Information

Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Antigen presentation by lung epithelial cells directs CD4⁺ T_RM cell function and regulates barrier immunity.