Activation of innate immunity by the leukotriene B 4 inhibits EBV induced B-cell transformation in cord-blood derived mononuclear cultures

Abstract

EBV specific cellular memory is not transferred from mother to child. By addition of the immunomodulators PSK and Trx80, that act on monocytes we could generate EBV-specific T cell response in cord-blood derived mononuclear cultures infected with the virus. In such cultures EBV infected B lymphocytes activated T and NK cells, and the immunostimulators activated the monocytes. Lymphokines produced by the monocytes induced the T and NK cells to progress into a functional activation state and they inhibited the EBV induced proliferation of B lymphocytes. Leukotrienes have been well studied in allergic and inflammatory responses, but less is known about their contribution to cellular immunity. In these experiments leukotriene LTB, produced by the activated monocytes was involved in the activation of effector cells. LTB 4 was detected in the culture supernatants and addition of LTB 4 biosynthesis inhibitors abolished the activation. These experiments showed thus that endogenously produced LTB 4 can induce effector cell responses. Addition of LTB 4 to the infected culture or readdition of LTB 4 treated monocytes to the culture of infected monocyte depleted cell population induced also T cell activation and led to inhibition of B cell proliferation. These results demonstrated thus that LTB 4 can contribute to the activation of innate immunity.