ICOS Costimulation Differentially Affects T Cells in Secondary Lymphoid Organs and Inflamed Tissues

Area of Science:

• Immunology
• Allergy and Autoimmunity

Background:

• B-cell and follicular helper T cell interactions typically occur in secondary lymphoid organs.
• The Inducible T-cell costimulator (ICOS) is crucial for B-cell responses and a potential target for autoimmune/allergic diseases.
• Inflamed tissues are emerging as sites for T-cell and B-cell interactions.

Purpose of the Study:

• To investigate the role of ICOS costimulation in T-cell/B-cell interactions within inflamed lung tissue.
• To compare ICOS function in both lung-draining lymph nodes and lung tissue using a mouse airway inflammation model.
• To assess the relative importance of dendritic cells and B cells as antigen-presenting cells (APCs) in this context.

Main Methods:

• Utilized a mouse model of airway inflammation.
• Compared immune reactions in the lung-draining lymph node and lung tissue.
• Assessed the impact of ICOS on T and B cell populations, B-cell differentiation, T follicular helper cells, and cytokine production.

Main Results:

• ICOS regulated antigen-specific T and B cell numbers and B-cell differentiation into germinal center(-like) cells in both lymph nodes and lung tissue.
• In lymph nodes, ICOS deficiency reduced T follicular helper cells but not Th2 cytokine production.
• In lung tissue, ICOS influenced Th2 cytokine production, with ICOS ligand expression on B cells being critical, but did not alter PD-1 expression on T cells.

Conclusions:

• ICOS differentially regulates effector T cells in secondary lymphoid organs versus inflamed tissues.
• The ICOS pathway is a viable target for modulating T-cell dependent B-cell responses at both sites.
• Understanding ICOS function in inflamed tissues is crucial for developing targeted therapies for allergic and autoimmune diseases.