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ICOS costimulates invariant NKT cell activation.
Hiroshi Kaneda1, Kazuyoshi Takeda, Tsuyoshi Ota
1Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Biochemical and Biophysical Research Communications
|January 5, 2005
Summary
Inducible T-cell costimulator (ICOS) significantly contributes to invariant natural killer T (iNKT) cell activation, alongside CD28. Blocking ICOS or CD28 pathways diminishes iNKT cell responses to alpha-galactosylceramide (alpha-GalCer).
Area of Science:
- Immunology
- Cellular Biology
Background:
- Invariant natural killer T (iNKT) cells are crucial immune cells activated by CD1d-restricted antigens.
- Costimulatory molecules CD80/86-CD28 and CD154-CD40 are known to be critical for iNKT cell activation.
Purpose of the Study:
- To investigate the role of Inducible T-cell costimulator (ICOS), a CD28 family member, in iNKT cell activation.
- To elucidate the independent and combined contributions of ICOS and CD28 pathways in iNKT cell responses.
Main Methods:
- Assessed constitutive and alpha-galactosylceramide (alpha-GalCer)-induced expression of ICOS and CD28 on iNKT cells.
- Utilized anti-ICOS ligand (B7RP-1) monoclonal antibody (mAb) and ICOS gene knockout to block ICOS-mediated costimulation.
- Evaluated the impact of blocking ICOS and/or CD28 pathways on alpha-GalCer-induced IFN-gamma and IL-4 production, cytotoxic activity, and anti-metastatic effects.
Main Results:
- iNKT cells constitutively express both ICOS and CD28, with ICOS expression upregulated post-alpha-GalCer treatment.
- Blockade of ICOS-mediated costimulation significantly inhibited alpha-GalCer-induced iNKT cell functions.
- Simultaneous blockade of ICOS-ICOS ligand and CD80/86-CD28 interactions largely abolished alpha-GalCer-induced immune responses.
Conclusions:
- ICOS plays a substantial and independent role in iNKT cell activation.
- iNKT cell activation is regulated by both CD28 and ICOS pathways independently.