Activation of Unusual Mac-1+CD4− CD8− T Cells Bearing αβ Antigen Receptor in Murine Lungs during Infection with Mycobacterium bovis BCG: Regulation by Interferon-γ

We have recently (Kawakami et al, Immunol. Lett. 1995;46: 143) demonstrated that unusual Mac-1⁺CD4^?CD8^? T cells bearing αβ antigen receptor (Mac-1⁺ αβ T cells) reside in a considerable proportion in murine lungs. The present study was performed to examine the dynamics of accumulation of these cells in the lungs following intravenous administration of Mycobacterium bovis BCG (BCG). Mac-1⁺ αβ T cells accumulated rapidly 24 hr after infection, followed by a gradual increase over the observation period of 15 days. Furthermore, the expression of Ia, ICAM-1 and FcγR II/III on their surface intensified dramatically after BCG infection. The kinetics of enhancement of Ia expression was slower than that of ICAM-1, with the maximum level attained in one day in the latter molecule but in two weeks in the former. Neutralization of endogenous IFN-γ by specific mAb completely blocked the augmented expression of Ia on Mac-1⁺ αβ T cells after BCG infection, but did not have any significant effect on that of ICAM-1. In contrast, in vivo administration of IFN-γ enhanced the expression of ICAM-1 as well as that of Ia. Our results indicate that accumulation of Mac-1 αβ T cells within the lung is associated with a differential change in the expression of surface antigens, and suggest that these cells may play a role in the host defense against mycobacterial infection.     

The IFN-γ-IDO1-kynureine pathway-induced autophagy in cervical cancer cell promotes phagocytosis of macrophage

Background: Cervical cancer is a common malignant disease in female patients accompanied by activation of autophagy in tumor cells. However, the exact regulatory factors of autophagy and its effects on the immune response remain unknown.Methods: The induction of autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine and epacadostat was detected by western blot analysis and by an autophagy detection kit. Following co-culture with pre-treated HeLa and SiHa cells, U937 cells were analyzed by flow cytometry to detect CD80, CD86, CD163 and CD206 expression and the induction of phagocytosis.Results: IFN-γ caused a significant increase in the autophagy levels of HeLa and SiHa cells by promoting indoleamine-2,3-dioxygenase-1 (IDO1) expression. The induction of phagocytosis in HeLa and SiHa cells and the expression levels of CD80 and CD86 in U937 cells were increased significantly following treatment with recombinant human IFN-γ. This effect was associated with the induction of tumor cell autophagy. IFN-γ treatment and IDO1 overexpression promoted tryptophan depletion and kynurenine accumulation in cervical cancer cells. The latter was more potent in inducing autophagy of cervical cancer cells and promoting phagocytosis of macrophages. In vivo, IDO1 overexpression restricted tumor growth in C57 mice and enhanced the induction of phagocytosis in macrophages.Conclusions: IFN-γ promoted induction of autophagy and macrophage phagocytosis in cervical cancer cells possibly via IDO1 expression and kynurenine metabolism.