CD4+ T cell persistence and function after infection are maintained by low-level peptide:MHC class II presentation

Area of Science:

• Immunology
• Microbiology
• Cellular Biology

Background:

• CD4(+) T cell populations typically decline after acute infections are cleared.
• Persistent infections controlled by T cells may offer unique insights into T cell stability.
• Salmonella infections are persistent phagocytic infections often managed by CD4(+) T cells.

Purpose of the Study:

• To investigate the stability of CD4(+) T cells during persistent Salmonella infection.
• To understand the mechanisms maintaining CD4(+) T cell populations in chronic infections.

Main Methods:

• Oral infection of mice with Salmonella.
• Enumeration and characterization of Salmonella-specific CD4(+) T cells over time.
• Assessment of T cell proliferation and function in secondary lymphoid organs.
• Adoptive transfer experiments to evaluate T cell behavior in different host environments.

Main Results:

• CD4(+) T cells specific for Salmonella peptide:MHC class II (MHCII) ligands were numerically stable for over one year post-infection.
• T cell stability was linked to ongoing proliferation driven by peptide:MHCII presentation in bacterial-harboring lymphoid organs.
• The persistent T cells were multifunctional Th1 cells that exhibited PD-1 expression and signs of exhaustion upon systemic antigen re-exposure.

Conclusions:

• Persistent Salmonella infection sustains a stable CD4(+) T cell population.
• Low-level, persistent peptide:MHCII presentation is crucial for maintaining these long-lived T cells.
• This contrasts with the typical decline of CD4(+) T cells after acute infections, highlighting a unique immune response to chronic challenges.