Effects of cyclosporin A on immunoglobulin production by EB virus stimulated lymphocytes.

Cyclosporin A (Cy A) enhances immunoglobulin (Ig) production by EB virus stimulated peripheral blood lymphocytes from normal subjects with prior immunity to EB virus. In 11 normal adults, this enhancement of Ig production correlated with T cell-mediated cytotoxic regression. Cultures from normal healthy adults without prior immunity showed a diminution of Ig production when Cy A was added. However, Cy A had no effect on Ig production by cord blood lymphocytes in the first week of culture but there was definite enhancement after 3 weeks. Cy A thus inhibits both the early phase of T cell help (which is lymphokine- or interferon-mediated) and the later phase of cytotoxicity manifested as regression. Furthermore, Cy A tended to inhibit IgG and IgA production in T depleted cultures, and had little effect on IgM or IgD, suggesting a differential effect on B cell subsets. These reactions to EB virus in vitro were investigated in two diseases in which EB virus immunity may be relevant. Six of 14 adult patients with primary hypogammaglobulinaemia showed no T cell-mediated regression nor Cy A enhancement, probably because of an underlying defect in both T and B cells. Regression was variable in 12 cases of rheumatoid arthritis, but Cy A initially diminished and later enhanced immunoglobulin production in all cases, suggesting a defect in the normal early response to EB virus in vitro.