Antigen presentation by murine splenic, but not hepatic, antigen-presenting cells to induce IL-2/IL-4 production from immune T cells is regulated by interactions between LFA-1/ICAM-1.

Pretransplant transfusion of multiple minor histoincompatible spleen cells to naive recipient mice by the portal vein suppresses the ability of those animals to reject skin grafts from mice syngeneic with those used for transfusion, and decreases in vitro immunity on rechallenge with the same antigens, by comparison with mice receiving transfusion by the lateral tail vein. We have shown elsewhere that this is correlated with a diminished activation of Th1 cells for IL-2 production, without apparently affecting activation of Th2 cells for IL-4 production. Similar data are obtained by merely infusing hepatic (vs. splenic) antigen-presenting cells (APC) into normal mice, or by challenging immune cells in vitro with antigen-pulsed hepatic (vs. splenic) APC. However, when antigen-pulsed splenic APC are incubated with immune T cells in the presence of anti-LFA-1 monoclonal antibody (Mab), selective activation of Th2 cells (as is seen with hepatic APC) again occurs at the expense of activation of Th1 cells. Anti-LFA-1 Mab causes little perturbation in lymphokine production from T cells stimulated with hepatic APC. Using cDNA probes for IL-2 and IL-4 we show that T-cell activation in the presence of anti-LFA-1 Mab leads to selective inhibition of transcription of IL-2 mRNA.