Submitted August 2, 2007
Accepted December 2, 2007
Leukotriene B4 activates T cells which inhibit B cell proliferation in EBV infected cord blood derived mononuclear cell cultures
Anquan Liu*, Hans-Erik Claesson, Yilmaz Mahshid, George Klein, and Eva Klein
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
Biolipox AB, Solna, Sweden
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
* Corresponding author; email: anquan.liu{at}ki.se.
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, PSK or Trx80 that activate monocytes, EBV specific 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 leukotriene 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 immunological effector function. This is orchestrated by complex cellular interactions, and autocrine loops mediated by soluble factors - here IFN-
, IL-15, IL-12 and LTB4. Importantly, the results indicate that endogenous LTB4 can induce T cell activation that inhibits the EBV induced proliferation of B lymphocytes.
