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CD4 and CD8 regulate interleukin 2 responses of T cells
K Takahashi1, M Nakata, T Tanaka
1Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Summary
CD4 and CD8 molecules negatively regulate T-cell interleukin 2 (IL-2) responses. This regulation involves crosslinking of CD4 and CD8, and the cytoplasmic kinase p56lck, suggesting a signaling pathway for T-cell inhibition.
Area of Science:
- Immunology
- Cell Biology
Background:
- T-cell activation and function are tightly regulated by surface molecules.
- Interleukin 2 (IL-2) is a critical cytokine for T-cell proliferation and survival.
Purpose of the Study:
- To identify T-cell surface molecules that regulate IL-2 responses.
- To elucidate the mechanism by which CD4 and CD8 influence IL-2 signaling.
Main Methods:
- Generation of inhibitory monoclonal antibodies (mAbs) against T-cell surface molecules.
- Transfection of IL-2-responsive cell lines with CD4 or CD8 cDNA.
- Testing the effect of anti-CD4 and anti-CD8 mAbs on IL-2 and IL-4 responses.
- Investigating the role of CD4/CD8 crosslinking and p56lck in the inhibitory mechanism.
Main Results:
- Specific inhibitory mAbs were directed against Lyt-2 (CD8 alpha).
- Anti-CD4 and anti-CD8 mAbs inhibited IL-2 responses in transfected cell lines and normal T-cell blasts.
- Inhibition was specific for IL-2 and dependent on CD4/CD8 crosslinking, not IL-2 binding.
- A mutant Lyt-2 molecule lacking the p56lck binding site could not mediate inhibition.
Conclusions:
- CD4 and CD8 molecules negatively regulate T-cell IL-2 responses.
- This negative regulation is mediated through a pathway involving cytoplasmic p56lck.
- CD4 and CD8 act as signaling molecules in the negative feedback loop of T-cell activation.