Soluble factors and the immune response: In vitro studies of the immunosuppression induced by the graft-versus-host reaction

Abstract

In vitro experiments were carried out to investigate the cause(s) of the immunosuppression induced by the graft-versus-host (GVH) reaction in F 1 hybrid mice injected with parental strain lymphoid cells. A modified Marbrook culture chamber, made up of two cell compartments separated by a cell impermeable membrane, was used in these studies. Spleen cells from either normal animals (NSC) or from animals experiencing a GVH reaction (GVH-SC) were cultured with sheep red blood cells (SRBC) and the direct plaque-forming cell (PFC) response to SRBC was measured. It was found that normal thymus, lymph node and spleen cells, separated from the GVH-SC by a cell impermeable membrane, restored partially or totally the immune response of the suppressed cells, while bone marrow cells did not. It was also found that GVH-SC inhibited the PFC response to SRBC of NSC when mixed in culture at a ratio of 1:5. Conversely the inhibitory effect of GVH-SC on the immune response of NSC was abrogated when the two cell populations were separated by a cell impermeable membrane. These observations demonstrate that GVH-induced immunosuppression is caused, at least in part, by the deficiency of a T-cell derived factor which is a necessary component of the normal immune response. It is suggested that the suppressive effect of GVH-SC on the immune response of NSC is mediated by a non-T cell which regulates the release and/or production of the T-cell derived factor.