Characteristic immunological tolerance in intrahepatic lymphocytes induced by bacterial superantigen SEB

We have reported that the liver is closely associated with the hematolymphoid system and that the liver, as a lymphoid organ, may play an important role in the differentiation of lymphocytes and oral tolerance. To investigate the relevance of the liver to immunological tolerance, we compared the response pattern to Staphylococcus enterotoxin B (SEB) in intrahepatic lymphocytes (IHL) with those of spleen cells (SPC) and mesenteric lymph node cells (mLNC) during tolerance induction. Tolerance was induced by i.v. injections of SEB in all three organs. IHL had a distinct pattern from the other cells in the induction of unresponsiveness to SEB. While SPC and mLNC have a proliferation phase before the reduction of DNA synthesis, IHL become tolerant immediately without this phase. When IHL became tolerant in the early period after SEB injection, their nylon-wool column non-adherent (NW-NA) IHL were not recovered from unresponsiveness in vitro in spite of the addition of irradiated normal SPC as accessory cells. NW-NA IHL did not secrete IL-2 during this process, indicating that NW-NA IHL were in a state of functional anergy soon after the i.v. administration of SEB. Phenotypic analysis revealed that the characteristic changes of IHL during the induction of unresponsiveness might be associated with the kinetic modulation of CD4+ V beta 8+ T cells. These results suggest that the liver may hold a different mechanism for the induction of tolerance to SEB from that of SPC and mLNC.