Human hybridoma suppressor factor (HSF) inhibits IL2 production in addition to suppressing immunoglobulin production.

Abstract

The human thymus cell hybridoma, 8E-24, secretes a potent immunosuppressive factor(s), HSF, which inhibits polyclonal immunoglobulin (Ig) production. Our current studies reveal that this suppression is monocyte dependent in that its suppressive activity for Ig production was not observed in monocyte-depleted lymphocyte cultures but was restored by addition of monocytes. The requirement for monocytes was equally satisfied by autologous or allogeneic monocytes or monocyte conditioned media. Although the suppression mediated by HSF required the presence of monocytes, the mechanism for monocyte participation appears to be different from that reported for suppression mediated by soluble immune response suppressor (SIRS) in that general oxygen free radical scavengers did not inhibit this activity. Further information on the mechanism of action of HSF was obtained from studies on its suppressive effect on the phytohemagglutinin(PHA)-induced proliferative response. In this system HSF significantly suppressed PHA induced interleukin 2(IL2) production of peripheral blood mononuclear cells (PBMC) in a dose dependent fashion without inhibiting the proliferative response of CTLL-20 target cells to IL2. Interleukin 1 (IL1) production by monocyte cultures was also not suppressed by HSF. These results indicate that HSF interferes with IL2 production and not its induction by IL1 or its interaction with the IL2 receptor. To investigate the role of HSF-induced IL2 suppression in the pokeweed mitogen (PWM) antibody synthesis assay, the time course of IgG, IgM, IL1, and IL2 production of PWM stimulated PBMC cultures was examined. Results showed that the peak of IL2 production occurred on the second day of culture and was significantly suppressed by HSF while IL1 production was not affected during the seven day culture period. Similar suppression of IL2 and IgM production was observed in cultures of B cells and T4+ cells. Reconstitution of the IL2 levels in these cultures with recombinant IL2 completely restored antibody production. These results suggest that HSF in the presence of monocytes modulates the function of T4+ cells by inhibiting IL2 production. The inhibition of IL2 production by HSF appears to be responsible for the suppression of antibody production.