ICOS is essential for effective T-helper-cell responses.

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Co-stimulatory signals modulate T-cell responses and are essential for adaptive immunity.
• Inducible co-stimulator (ICOS) is a T-cell expressed co-stimulator homologous to CD28.
• ICOS specifically binds B7RP-1 and provides co-stimulatory signals.

Purpose of the Study:

• To investigate the in vivo physiological function of ICOS.
• To determine the role of ICOS in T-cell dependent B-cell responses and antibody production.

Main Methods:

• Generation and characterization of gene-targeted ICOS-deficient mice.
• Assessment of T-cell dependent B-cell responses, germinal center formation, and immunoglobulin class switching in vivo.
• Analysis of cytokine production (interleukin-4 and interferon-gamma) by ICOS-deficient T cells in vitro.

Main Results:

• ICOS deficiency resulted in severely impaired T-cell dependent B-cell responses.
• Germinal center formation and immunoglobulin class switching, including IgE production, were defective in ICOS-deficient mice.
• ICOS-deficient T cells produced low levels of interleukin-4 but normal levels of interferon-gamma upon restimulation.

Conclusions:

• ICOS provides an essential co-stimulatory signal for efficient T-cell and B-cell interaction.
• ICOS is critical for normal antibody responses to T-cell dependent antigens.
• ICOS plays a significant role in regulating T-cell cytokine production and adaptive immunity.