Rats recovering from a systemic graft-vs.-host reaction (GVHR) possess factors in the serum which can inhibit the production of a local GVHR. After incubation in vitro for 1 h at 37 degrees C these factors reduce the GVH-producing potential of parental spleen or lymph node cells to 24% of control cells treated with normal serum. These factors appear within 1 wk after initiation of a systemic GVHR and some residual activity persists for up to 8 mo. The serum activity was present in the globulin fraction and was completely removed by absorption with spleen, lymph node, or kidney homogenates from either parental strain rats. These studies indicate that during the course of a systemic GVHR, serum factors directed against the host appear in the circulation and tend to inhibit the production of further GVHR by a second challenge of either parental strain cells.

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