Prevention of human helper T-cell clone activation by cyclosporin A also blocks secretion of granulocyte/macrophage colony stimulating activity.

Cyclosporin A (CsA) blocks stimulation and growth of alloreactive T helper cell clones (Th-TCC), even in the presence of exogenous Interleukin-2 (IL-2). To examine whether this might reflect a generalised inhibition of cytokine production by these cells, their production of granulocyte/macrophage colony-stimulating factors (GM-CSF), thought not to be involved in the autocrine proliferation of the clones themselves, was investigated. Contrary to the prediction that only pathways relevant to T cell clonal expansion would be blocked by CsA, it was found that this immunosuppressive substance exerted a profound inhibitory activity on GM-CSF secretion, even in the presence of exogenous IL-2. Although a higher concentration of CsA was required to block GM-CSF secretion than to block proliferation, the former was not due to toxic effects on the cells, or permanently switching off the genes for GM-CSF, since upon further cultivation of the clones without CsA, alloantigen-specific responsiveness was restored. These results therefore show that clonal human T helper cell populations are sensitive to inhibition of GM-CSF secretion by CsA. Part of the immunosuppressive mechanism of action of CsA may therefore reside in this activity, since blockade of GM-CSF secretion by T helper cells would influence functional activities of antigen presenting cells.