T-cell co-stimulation through B7RP-1 and ICOS

Area of Science:

• Immunology
• Molecular Biology

Background:

• T-cell activation relies on co-stimulation via receptors like CD28 and antigen-specific signaling through the T-cell receptor.
• A new costimulatory receptor-ligand pair related to the CD28-B7 pathway is investigated.

Purpose of the Study:

• To identify and characterize a novel costimulatory receptor-ligand pair involved in T-cell activation.
• To elucidate the role of ICOS and B7RP-1 in the adaptive immune response.

Main Methods:

• Identification and characterization of the ICOS receptor and its ligand, B7RP-1.
• In vitro co-stimulation assays of T cells using B7RP-1.
• In vivo studies using transgenic mice expressing a B7RP-1-Fc fusion protein and sensitized mice treated with B7RP-1-Fc.

Main Results:

• The novel receptor, ICOS, is expressed on activated and memory T cells, while its ligand, B7RP-1, is found on B cells and macrophages.
• ICOS and B7RP-1 function independently of the CD28-B7 pathway, with B7RP-1 demonstrating in vitro T-cell co-stimulation.
• Transgenic mice exhibited lymphoid hyperplasia, and treated mice showed enhanced hypersensitivity, indicating in vivo co-stimulatory activity.

Conclusions:

• ICOS and B7RP-1 constitute a new, distinct costimulatory receptor-ligand pair structurally related to CD28-B7.
• This pathway plays a significant role in regulating T-cell responses and the adaptive immune system.