Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood derived mononuclear cell cultures

Abstract

Epstein-Barr virus (EBV)-specific cellular memory is not transferred from mother to child. Therefore, EBV-induced B-cell proliferation in in vitro-infected cord blood mononuclear cell cultures is not inhibited. However, by addition of immunomodulators, polysaccharide K (PSK) or truncated thiore-doxin (Trx80) that activate monocytes, EBV-specif ic T-cell response could be generated in such cultures. Presently, we demonstrate that leukotriene B4 (LTB4) is involved in the effect of the immunomodulators. LTB4 was detected in the medium, and T-cell activation was compromised by addition of leuko-triene biosynthesis inhibitors. Moreover, we found that LTB4 added to infected cultures, which did not receive the immunomodulators, induced functional activation of the T cells. LTB4 activated the monocytes and acted directly on the T cells. In consequence, addition of LTB4 inhibited the EBV-induced proliferation of B lymphocytes. Specific cytotoxicity could be generated by restimulation of the T cells. The experiments showed successive stages of T-cell activation in acquisition of their immunologic effec-tor function. This is orchestrated by complex cellular interactions, and autocrine loops mediated by soluble factors-here interferon (IFN)-γ, interleukin (IL)-15, IL-12, and LTB 4. Importantly, the results indicate that endogenous LTB4 can induce T-cell activation that inhibits the MEBV-induced proliferation of B lymphocytes. © 2008 by The American Society of Hematology.