Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood-derived mononuclear cell cultures.
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 thioredoxin (Trx80) that activate monocytes, EBV-specific T-cell response could be generated in such cultures. Presently, we demonstrate that leukotriene B(4) (LTB(4)) is involved in the effect of the immunomodulators. LTB(4) was detected in the medium, and T-cell activation was compromised by addition of leukotriene biosynthesis inhibitors. Moreover, we found that LTB(4) added to infected cultures, which did not receive the immunomodulators, induced functional activation of the T cells. LTB(4) activated the monocytes and acted directly on the T cells. In consequence, addition of LTB(4) 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 effector function. This is orchestrated by complex cellular interactions, and autocrine loops mediated by soluble factors-here interferon (IFN)-gamma, interleukin (IL)-15, IL-12, and LTB(4). Importantly, the results indicate that endogenous LTB(4) can induce T-cell activation that inhibits the EBV-induced proliferation of B lymphocytes.
Liu
Anquan
A
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm, Sweden. anquan.liu@ki.se
Claesson
Hans-Erik
HE
Mahshid
Yilmaz
Y
Klein
George
G
Klein
Eva
E
D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D020031:Epstein-Barr Virus Infections; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D037181:Lectins, C-Type; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016260:Monocytes, Activated Killer / Q000187:drug effects / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D018102:Receptors, Leukotriene B4 / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013879:Thioredoxins / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D037181:Lectins, C-Type; D007975:Leukotriene B4; D010446:Peptide Fragments; D011135:Polysaccharides, Bacterial; D018102:Receptors, Leukotriene B4; D013879:Thioredoxins; D000099192:CD69 Antigens; C513240:LTB4R protein, human; C427943:Trx80 protein, human