Peripheral and lung resident memory T cell responses against SARS-CoV-2

Area of Science:

• Immunology
• Virology
• Respiratory Medicine

Background:

• Resident memory T cells (T_RM) in the respiratory tract are vital for controlling SARS-CoV-2.
• T_RM cells are largely non-circulating, limiting their assessment in blood during migration to lung tissue.

Purpose of the Study:

• To characterize circulating virus-specific T cell responses during acute SARS-CoV-2 infection.
• To correlate these responses with clinical outcomes and identify markers of disease severity.
• To investigate the persistence of T_RM cells in the lungs and their relationship with blood T cell profiles post-infection.

Main Methods:

• Analysis of circulating virus-specific T cell responses, including functional, migratory, and apoptotic patterns.
• Assessment of T cell responses against specific SARS-CoV-2 viral proteins (S and N peptides).
• Measurement of cytokine production (IFNγ, IL-4, IL-12p70, IL-10) and CCR7 expression in T cells.

Main Results:

• Disease severity correlated with IFNγ/IL-4 responses, S peptide reactivity, and apoptosis.
• Non-hospitalized patients showed higher IL-12p70, N peptide-induced degranulation, and IL-10-secreting CCR7⁺ T cells.
• Lung T_RM cells were detected up to 10 months post-infection, with blood profiles not mirroring tissue-resident status.

Conclusions:

• A balanced anti-inflammatory antiviral response is associated with better COVID-19 outcomes.
• Persistent T_RM cells in the lungs are important for sustained protection against SARS-CoV-2.
• Circulating T cell patterns during acute infection provide insights into disease trajectory and long-term immunity.