Complement in Graft Versus Host Disease: I. Depletion of Complement Components during a Systemic Graft Versus Host Reaction in the Rat 1

Summary

Serum complement (C) and C components were examined during a systemic graft versus host (GVH) reaction in the rat. In our series of experiments (Lewis × Brown Norway) F₁ hybrid rats (60-80g) were given 200 × 10⁵ or 400 × 10⁵ Lewis spleen cells intravenously. Clinical GVH disease appeared 5-7 days after cell injection. Five of six rats in the experimental groups had a fall in levels of serum C2 (20-76 %) and C4 (75-98%). Only one of six rats in the control group had a significant fall in C components.

In a subsequent experiment (Fischer 344 × Brown Norway) F₁ hybrid rats (60g) were given 400 × 10⁶ Fischer 344 spleen cells or 200 × 10⁶ Fischer 344 Ficoll-Hypaque separated spleen lymphocytes. Clinical GVH disease in this instance appeared on day 10. As in the previous experiments C2 and C4 fell markedly, 20-60% and 60-80%, respectively, from baseline titers. The control groups did not have a significant fall in C2 or C4. Further examination showed reduction in C3, C5, C6 and C8 suggesting a sequential activation of the C system via the classical pathway.

We have postulated that the cells undergoing blast transformation may be activating the C system through membrane changes during the GVH reaction. Furthermore, the deficiency of C and C components during GVH disease may contribute to the increased susceptibility of the host to infection and sepsis.

We wish to thank M. Ramnaraine for her excellent technical assistance.