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CD4+ tissue-resident memory T cells and their role in immunity
Margarida Kirkby1, Marc Veldhoen1,2
1Gulbenkian Institute for Molecular Medicine (GIMM), Lisbon, Portugal.
Immunology and Cell Biology
|July 25, 2025
Summary
CD4+ tissue-resident memory T (TRM) cells are crucial for lung immunity. This review explores their roles in fighting infections, causing inflammation, and their potential for developing effective vaccines against respiratory pathogens.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- CD4+ tissue-resident memory T (TRM) cells are vital for lung immune protection against pathogens.
- Unlike circulating cells, CD4+ TRM cells reside in lung tissues, offering rapid local responses.
- Their specific functions and subsets are less understood compared to CD8+ TRM cells.
Purpose of the Study:
- To review the differentiation, maintenance, and immunological roles of CD4+ TRM cells in the lungs.
- To highlight the involvement of CD4+ TRM cells in various infections and inflammatory conditions.
- To discuss the potential of CD4+ TRM cells in vaccine development for respiratory diseases.
Main Methods:
- Literature review focusing on CD4+ TRM cell research.
- Analysis of studies on TH1, TH2, TH17, and TRH subsets.
- Examination of vaccine strategies targeting lung CD4+ TRM cells.
Main Results:
- CD4+ TRM cells encompass diverse subsets (TH1, TH2, TH17, TRH) contributing to immunity against viruses, bacteria, and fungi.
- These cells enhance immune responses and antibody production during infections but are also linked to chronic inflammation and allergies.
- Mucosal vaccination, particularly intranasal delivery, effectively generates lung CD4+ TRM cells, showing promise for long-term protection.
Conclusions:
- CD4+ TRM cells are critical players in both protective immunity and pathogenesis within the lung.
- Understanding their subsets and functions is key to harnessing their potential for therapeutic interventions.
- Targeting CD4+ TRM cell induction via mucosal vaccines offers a promising strategy for controlling respiratory infections.
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