Abstract 228

Background: Stimulation with IFN-γ upregulates molecules of the B7-family on Mφ, which allow them to provide costimulatory signals for T cell activation. Evidence that Mφ can destroy T cells comes from the studies with coreceptor-specific antibodies. Mφ recognize αCD4 mAb and destroy targeted T cells in a CD95-dependent pathway. Aims: We addressed the question, how preincubation of Mφ with IFN-γ may functionally influence the deletion of T cells. Methods: Isolated Mφ from healthy adults were stimulated with IFN-γ for 24h and washed twice prior to coincubation with Mφ-depleted T-cells and a cytophilic αCD4 mAb. T cell-subpopulations were stained fluorometrically with non-crossreactive antibodies. Results: Compared to untreated Mφ, preincubation with IFN-γ leads to an upregulation of B7-1 and B7-2 on Mφ and to a 50% decreased fraction of deleted CD4 T cells after coincubation with αCD4 mAb. The addition of a neutralizing αIFN-γ mAb inhibits IFN-γ-mediated effects on Mφ, enhances T cell-deletion in the non-preincubated group and partially reverts the IFN-γ-effects in the preincubated group. Conclusion: These results suggest an altered T cell deletion after IFN-γ mediated Mφ-activation and thus may have relevance in the perpetuation of T cell activation e.g. following infection.