Significant contribution of spleen cells in mediating the lethal effects of endotoxin in vivo

Abstract

Two closely related, histocompatible mouse strains that have marked differences in in vitro and in vivo responses to endotoxin were used to evaluate the contribution of lymphoid cells to the lethal effect of [Salmonella typhimurium and Escherichia coli] endotoxin. C3H/HeJ mice are endotoxin resistant; C3H/HeN mice are endotoxin sensitive. In vitro spleen cell mitogenic responses to endotoxin were similar in untreated mice and in mice that received sublethal irradiation (450 R) followed by reconstitution with autologous spleen cells. Reconstitution with spleen cells from the related strain produced chimeric animals with spleen cell mitogenic activity like that of the donor strain. When chimeric animals were subjected to a lethal challenge of endotoxin, their response was markedly altered by the transferred lymphoid cells. C3H/HeJ animals reconstituted with C3H/HeN cells became more endotoxin sensitive; C3H/HeN animals reconstituted with C3H/HeJ cells became more endotoxin resistant. Spleen cells apparently play a significant, detrimental role in endotoxin-induced lethality.