Flaishon Liat, Topilski Ian, Shoseyov David, Hershkoviz Rami, Fireman Elizabeth, Levo Yoram, Marmor Sylvia, Shachar Idit
Department of Immunology, Weizmann Institute of Science, and Sourasky Medical Center, Tel-Aviv, Israel.
J Immunol. 2002 Apr 15;168(8):3707-11. doi: 10.4049/jimmunol.168.8.3707.
Activation of naive T and B cells occurs only within the context of organized lymphoid tissue. Thus, the continuous recirculation of mature lymphocytes is crucial for the development of primary immune response to foreign Ags. We have previously shown that low levels of IFN-gamma inhibit homing of B cells to the secondary lymphoid organs. In this study, we demonstrate that similarly low doses of IFN-gamma down-regulate integrin-mediated adhesion and migration of naive T and Th2 cells, and have a profound effect on the in vivo homing of naive T cells to the lymph nodes. Moreover, we show that these low doses of IFN-gamma have anti-inflammatory effects in an in vivo asthma model. Thus, in contrast to the proinflammatory effects of IFN-gamma at relatively high concentrations, low dose IFN-gamma appears to exert global suppressory effects on T cell trafficking and may have clinical application as an anti-inflammatory agent.
初始T细胞和B细胞的激活仅发生在有组织的淋巴组织环境中。因此,成熟淋巴细胞的持续再循环对于对外源抗原产生初级免疫反应至关重要。我们之前已经表明,低水平的干扰素-γ会抑制B细胞归巢至次级淋巴器官。在本研究中,我们证明,同样低剂量的干扰素-γ会下调整合素介导的初始T细胞和Th2细胞的黏附和迁移,并对初始T细胞在体内归巢至淋巴结产生深远影响。此外,我们表明,这些低剂量的干扰素-γ在体内哮喘模型中具有抗炎作用。因此,与相对高浓度时干扰素-γ的促炎作用相反,低剂量干扰素-γ似乎对T细胞迁移发挥全面的抑制作用,并且可能作为一种抗炎剂具有临床应用价值。