Immune checkpoint molecule TIGIT manipulates T cell dysfunction in septic patients

Area of Science:

• Immunology
• Infectious Diseases
• Critical Care Medicine

Background:

• Sepsis involves a dysregulated host response to infection, leading to T cell dysfunction.
• While PD-1 is a known target, other coinhibitory receptors' roles in sepsis are unclear.
• T cell dysfunction contributes to pathogen persistence, nosocomial infections, and mortality in sepsis.

Purpose of the Study:

• To investigate the role of the immune checkpoint molecule TIGIT in T cell regulation during sepsis.
• To assess TIGIT as a potential predictor of sepsis prognosis and a therapeutic target.

Main Methods:

• Prospective enrollment of 50 sepsis patients and 17 healthy donors.
• Quantification of TIGIT and other molecule expression on lymphocytes via flow cytometry.
• Ex vivo functional assays and TIGIT blockade with anti-TIGIT antibody.

Main Results:

• TIGIT expression was significantly upregulated on T cells in sepsis and septic shock patients.
• Elevated TIGIT+ T cells correlated with increased inflammation and organ injury.
• TIGIT expression on CD8+ T cells predicted ICU mortality; TIGIT+ T cells showed impaired function.
• Anti-TIGIT antibody treatment restored cytokine production in T cells from septic patients.

Conclusions:

• TIGIT is upregulated on T cells in sepsis and correlates with disease severity and mortality.
• TIGIT functions as a clinical predictor for poor prognosis in sepsis.
• TIGIT represents a potential therapeutic target for novel immunotherapies in sepsis.
• Blocking TIGIT can restore T cell function, offering a promising avenue for sepsis treatment.