Anti CD4 antibodies directly suppress TNF-α production in human Th1 T-cell clones but not IL-4 production in Th2 clones

Background

Anti-CD4 antibodies have been described for treatment of certain autoimmune diseases. In vitro experiments have shown that anti-CD4 antibodies are able to inhibit immune responses mediated by T helper cells.

Objective

However, it became unclear whether or not these experiments performed in bulk cultures represent merely regulatory effects or cell biological differences between functionally different populations of T helper cells.

Methods

Therefore, we established human Th1 T-cell and Th2 T-cell clones, which were treated with anti-human CD4 antibodies. The T-cell clones were stimulated via the T-cell receptor and the CD28 molecule, and cytokine production was determined for TNF-α, IFN-γ and IL-4.

Results

TNF-α and Interferon-γ are produced exclusively by Th1-T cells and inhibition of cytokine production by anti-CD4 was nearly total for TNF-α production but much less pronounced for IFN-γ. No effect of anti-CD4 on IL-4 production in human Th2 T-cell clones was observed.

Conclusion

Our data may help us to understand the mechanisms of anti-CD4-mediated modulation of immune responses.