T cell Ig mucin 3 (Tim-3) has been found to play an important role in Th1-mediated auto- and alloimmune responses, but the function of soluble form of Tim-3 (sTim-3) remains to be elucidated. In this study, we report the inhibitory effect of sTim-3 on T cell-mediated immune response. In this study, sTim-3 mRNA was found, among different tissues and organs, only in splenic cells, and the activation of splenocytes resulted in up-regulated production of both sTim-3 mRNA and protein. We constructed a eukaryotic expression plasmid, psTim-3, which expresses functional murine sTim-3. In C57BL/6 mice inoculated with B16F1 melanoma cells, the growth of tumor was facilitated by the expression of this plasmid in vivo. Furthermore, sTim-3 inhibited the responses of T cells to Ag-specific stimulation or anti-CD3 mAb plus anti-CD28 mAb costimulation and the production of cytokines IL-2 and IFN-γ in vitro. In tumor rejection model, sTim-3 significantly impaired T cell antitumor immunity, evidenced by decreased antitumor CTL activity and reduced amount of tumor-infiltrating lymphocytes in tumor. Real-time PCR analysis of gene expression in tumor microenvironment revealed the decreased expression of Th1 cytokine genes and the unchanged profile of the genes related to T regulatory cell function, suggesting that the inhibitory effect of sTim-3 on the generation of Ag-specific T cells in vivo is dominated by T effector cells rather than T regulatory cells. Our studies thus define sTim-3 as an immunoregulatory molecule that may be involved in the negative regulation of T cell-mediated immune response.

In this paper, a space vector pulse width modulation (SVPWM) algorithm is proposed, which is in α β frame with dclink capacitor voltage equalization for diode-clamped multilevel converters (DCMC). The α β frame is a coordinate system similar to αβ frame. In this frame, some original complex calculations are substituted by integer additions, integer subtractions, and truncations, etc.. It brings the time and area efficiency to fix-point digital realization, especial for the application in field programmable gate array. Meanwhile, a minimum energy property of multiple dc-link capacitors is applied as the basic principle for voltage equalization based on a capacitor current prediction algorithm. By evaluating the redundant vectors in each pulse dwelling period, the balancing algorithm chooses an optimal vector, generates the optimal PWM signals, and sustains the voltage stable. After that, an arbitrary multilevel SVPWM intellectual property (IP) core is designed and analyzed in the α β frame. At the end of this article, a 5-level DCMC-based static synchronous compensator is built and tested. The experimental results the balancing algorithm and the system steady-state and dynamic performances.Index Terms-Space vector pulse width modulation (SVPWM), voltage equalization, diode-clamped multilevel converter (DCM-C), static synchronous compensator (STATCOM).

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