ICOS is critical for T helper cell-mediated lung mucosal inflammatory responses

Area of Science:

• Immunology
• Cellular Immunology
• T cell biology

Background:

• T helper (TH) cells are crucial for adaptive immunity.
• Costimulatory molecules CD28 and ICOS play roles in T cell activation and function.
• Understanding their distinct and cooperative roles is essential for immune response modulation.

Purpose of the Study:

• To investigate the individual and combined requirements for CD28 and ICOS in vivo.
• To elucidate the specific roles of CD28 and ICOS in T helper cell priming and effector responses.
• To determine how these molecules influence T cell expansion, cytokine production, and migration.

Main Methods:

• In vivo studies using blocking agents like CTLA-4-Ig and ICOS-Ig.
• Administration of a neutralizing ICOS monoclonal antibody.
• Analysis of T cell expansion, TH2 cytokine production, and eosinophilic inflammation.
• Assessment of T cell migration through chemokine receptor expression.

Main Results:

• Both CD28 and ICOS are critical for effective T helper cell responses.
• Inhibition of CD28 or ICOS signaling attenuated T cell expansion, TH2 cytokine production, and eosinophilic inflammation.
• CD28 signaling is essential during the initial priming phase of T cells.
• ICOS signaling, via its ligand B7RP-1, regulates T cell effector functions and chemokine receptor upregulation, influencing T cell migration.

Conclusions:

• CD28 and ICOS play distinct yet cooperative roles in regulating immune responses.
• CD28 acts primarily during T cell priming.
• ICOS is crucial for regulating T cell effector functions and migration, impacting the overall outcome of the immune response.