Intracellular signal transduction of activated T cells and anergic T cells

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Human T cells show different biological responses according to T-cell maturation or subsets when stimulated with bacterial superantigens. We addressed the question why the T cells response in different way by comparing signal transduction.1. Human thymic CD1a^-CD4^+ T cells in the final stage of thymic maturation are susceptible to anergy induced by bacterial superantigens, whereas adult peripheral blood (APB) CD4^+ T cell are not only induced to anergic state but also exhibit high responses by restimulation. The tyrosine kinase activity of lck increased after restimulation in APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. The Lck was highly tyrosinphosphorylated in both types of T-cell blasts before restimulation. After restimulation, it was markedly dephosphorylated in APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. Confocal microscopy demonstrated that colocalization of Lck and CD45 was induced in restimulated APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. Further, remarkable accumulation of Lck in the membrane raft was observed in restimulated APB CD4^+ T-cell blasts but not in thymic CD4^+ T-cell blasts. These data indicate that interaction between Lck and CD45 is important for T- cell activation and that the interaction is suppressed physically in thymic CD4^+ T-cell blasts and plays a critical role in sustaining an anergic state.2. Next, we examined superantigen-induced responses of APB CD4^+ and CD8^+ T-cell subsets in vitro. The proliferative response and IL-2/IL-4 production were higher in CD4^+ T-cell subset than in CD8^+ T-cell subset, while IFN-y production and cytotoxic activity on MHC class II^+ cells were higher in the CD8^+ subset than in the CD4^+ subset. These data indicate that CD4^+ and CD8^+ 1-cell subsets are activated by bacterial superantigens in specific ways. Now we try to confirm that Lck regulation is related with the different responses.