Cyclosporin A inhibits a discrete step in T-lymphocyte stimulation

Cyclosporin A (CyA) interferes with immune responses and prevents growth factor release by stimulated T cells. However, it is not known whether this is due to an effect on the accessory cells, required for T-cell responses, whether antigen recognition cannot occur, or whether later steps, leading to lymphokine production, are blocked. For this reason, the effect of CyA on homogeneous populations of T tumour cells was investigated. The immunosuppressive compound efficiently prevented T-cell growth factor (TCGF) (interleukin 2) release by stimulated tumour cells. Still, the cells retained the surface antigen T3, known to be involved in T-cell stimulation, after treatment with CyA. Furthermore, CyA failed to affect the inhibition of proliferation, observed in a T-cell tumour in response to stimulation, indicating that the cells had received the stimulatory impetus, TCGF release, induced by treatment with a phorbol ester, was only partly sensitive to inhibition by CyA, demonstrating that CyA will interfere with discrete aspects of the stimulation of a T-cell.