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ICOS co-stimulatory receptor is essential for T-cell activation and function
C Dong1, A E Juedes, U A Temann
1Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|May 9, 2001
Summary
Inducible co-stimulatory molecule (ICOS) is crucial for T-cell activation, proliferation, and antibody production. ICOS deficiency impairs immune responses and increases susceptibility to autoimmune diseases.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- T-lymphocyte activation and immune function depend on co-stimulatory molecules like CD28 and CTLA4.
- The inducible co-stimulatory molecule (ICOS) is expressed on activated T cells and plays a role in immune responses.
- The ligand for ICOS, B7H/B7RP-1, is found on B cells and in non-immune tissues.
Purpose of the Study:
- To investigate the role of ICOS in T-cell activation and immune function.
- To analyze the effects of ICOS deficiency on immune responses and autoimmune disease susceptibility.
Main Methods:
- Generation and analysis of ICOS-deficient (ICOS-/-) mice.
- Assessment of T-cell activation, proliferation, and cytokine production (interleukin-4).
- Evaluation of humoral immune responses and experimental autoimmune encephalomyelitis.
Main Results:
- T-cell activation and proliferation were defective in ICOS-/- mice.
- ICOS-/- T cells failed to produce interleukin-4 in vitro and in vivo.
- ICOS deficiency impaired humoral immune responses to various antigens.
- ICOS-/- mice exhibited increased susceptibility to experimental autoimmune encephalomyelitis.
Conclusions:
- ICOS is essential for effective T-cell activation, proliferation, and interleukin-4 production.
- ICOS plays a critical role in humoral immunity.
- ICOS has a protective function in inflammatory autoimmune diseases.
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