Two sides of the same coin: Protective versus pathogenic CD4⁺ resident memory T cells

Area of Science:

• Immunology
• Cellular Biology
• Infectious Diseases

Background:

• Adaptive immunity relies on memory for secondary infection defense.
• Resident memory T cells (T_RM) are tissue-resident immune cells distinct from circulating memory T cells.
• Research has predominantly focused on CD8⁺ T_RM, with less attention paid to CD4⁺ T_RM.

Purpose of the Study:

• To review the key features of CD4⁺ T_RM in both healthy and diseased states.
• To explore the protective and pathogenic roles of CD4⁺ T_RM.
• To discuss CD4⁺ T_RM contributions to SARS-CoV-2 immunity and COVID-19 immunopathology.

Main Methods:

• Literature review of existing research on T_RM, particularly CD4⁺ T_RM.
• Analysis of functional and transcriptional distinctions between T_RM subsets.
• Synthesis of evidence regarding CD4⁺ T_RM involvement in viral, bacterial, fungal, and parasitic infections.

Main Results:

• CD4⁺ T_RM are abundant in tissues and exhibit diverse polarization capabilities.
• Emerging evidence indicates CD4⁺ T_RM can mediate both protective immunity and disease pathogenesis.
• CD4⁺ T_RM play a role in SARS-CoV-2 infection, potentially contributing to COVID-19 immunopathology.

Conclusions:

• CD4⁺ T_RM are critical immune players with complex roles in tissue-specific immunity.
• Understanding CD4⁺ T_RM function is essential for developing effective strategies against infectious diseases like COVID-19.
• Further research into CD4⁺ T_RM subsets and their polarization is warranted.