Hepatitis C virus（HCV）-specific CD8^＋ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the vi...Hepatitis C virus（HCV）-specific CD8^＋ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 （PD-1）. This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8^＋ T cells are exhausted with impairment of several effector mechanisms, such as： type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand （PD-L1）. After this blockade, HCV-specific CD8^＋ T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-l-expressing intrahepatic HCV-specific CD8^＋ T cells do not restore their effector abilities after PD-1/ PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gClq receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response aclainst HCV to succeed in clearing the infection.展开更多
We read the original article by Nuis, et al. and the reply by Dogan, et al. with great interest. Nuis, et al. examined whether transcatheter aortic valve implantation （TAVI） in patients suffering from severe aortic ...We read the original article by Nuis, et al. and the reply by Dogan, et al. with great interest. Nuis, et al. examined whether transcatheter aortic valve implantation （TAVI） in patients suffering from severe aortic stenosis led to changes in corrected QT dispersion （cQTD）, previously used to predict arrhythmic risk. Dogan, et al. proposed that a different marker, transmural dispersion of repolariza- tion （TDR）, has better accuracy in risk prediction.展开更多
A new researching method on clothing comfort perception is developed.By it the skin surface temperature changes and subjective psychological perception of human body sections stimulated by the same cold stimulation ar...A new researching method on clothing comfort perception is developed.By it the skin surface temperature changes and subjective psychological perception of human body sections stimulated by the same cold stimulation are studied.With the multiple comparison analysis method the changing laws of skin temperature of main human body sections is obtained.展开更多
To investigate whether estradiol （E2） plays a role in cell-contact-dependent regulatory mechanism of T cell activation, we studied the role of E2 in regulating gene transcription of CTLA-4, ICOS, B7-1, B7-2 and B7h ...To investigate whether estradiol （E2） plays a role in cell-contact-dependent regulatory mechanism of T cell activation, we studied the role of E2 in regulating gene transcription of CTLA-4, ICOS, B7-1, B7-2 and B7h in vitro. The splenic cells of normal female BALB/c mice were activated by ConA. Then the cells were cultured with E2 （100 pg/ml or 50 ng/ml） for 24 h or 48 h, respectively. The cell proliferation was measured by MTF assay and the expression of the co-stimulatory molecules mRNA was examined by RT-PCR analysis. We found that E2 （100 pg/ml, physiological level） stimulated the acti- vated spleen cells proliferation; inhibited CTLA-4, ICOS, TGF-β and IL-10 gene transcription; promoted B7-1 and B7-2 gene transcription. E2 （50 ng/ml, pregnant level） inhibited the proliferation of the activated splenic cells; promoted CTLA-4, B7-1, IL-10 but inhibited B7-2 and TGF-β gene transcription. Therefore, we conclude that the effects of E2 on T cell activation are partially through its regulation on the co-stimulatory molecules. The co-stimulatory molecules are crucial components of the cell-contact dependent regulatory mechanism, and E2 may regulate T cell activation by this mechanism.展开更多
基金Supported by Grants from "Fiscam" J.C.C.M (Ayuda para proyectos de investigación en salud PI-2007/32)+5 种基金"Fundación de Investigación Médica Mutua Madrileń a" (Beca Ayudas a la Investigación FMMM 2548/2008) from SpainBenito-Martínez S was supported by a research grant from "Fiscam" J.C.C.M ("Perfeccionamiento y movilidad de investigadores" MOV-2007_JI/18), SpainCalvino M was supported by a research grant from "Instituto de Salud Carlos III" (Contrato de apoyo a la investigación en el SNS’’ CA07/00157), Spain
文摘Hepatitis C virus（HCV）-specific CD8^＋ T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 （PD-1）. This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8^＋ T cells are exhausted with impairment of several effector mechanisms, such as： type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand （PD-L1）. After this blockade, HCV-specific CD8^＋ T cells reacquire their functionality. Nevertheless, functional restoration depends on PD-1 expression level. High PD-l-expressing intrahepatic HCV-specific CD8^＋ T cells do not restore their effector abilities after PD-1/ PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gClq receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response aclainst HCV to succeed in clearing the infection.
文摘We read the original article by Nuis, et al. and the reply by Dogan, et al. with great interest. Nuis, et al. examined whether transcatheter aortic valve implantation （TAVI） in patients suffering from severe aortic stenosis led to changes in corrected QT dispersion （cQTD）, previously used to predict arrhythmic risk. Dogan, et al. proposed that a different marker, transmural dispersion of repolariza- tion （TDR）, has better accuracy in risk prediction.
基金Supported by the national education ministry key research project 02107
文摘A new researching method on clothing comfort perception is developed.By it the skin surface temperature changes and subjective psychological perception of human body sections stimulated by the same cold stimulation are studied.With the multiple comparison analysis method the changing laws of skin temperature of main human body sections is obtained.
文摘To investigate whether estradiol （E2） plays a role in cell-contact-dependent regulatory mechanism of T cell activation, we studied the role of E2 in regulating gene transcription of CTLA-4, ICOS, B7-1, B7-2 and B7h in vitro. The splenic cells of normal female BALB/c mice were activated by ConA. Then the cells were cultured with E2 （100 pg/ml or 50 ng/ml） for 24 h or 48 h, respectively. The cell proliferation was measured by MTF assay and the expression of the co-stimulatory molecules mRNA was examined by RT-PCR analysis. We found that E2 （100 pg/ml, physiological level） stimulated the acti- vated spleen cells proliferation; inhibited CTLA-4, ICOS, TGF-β and IL-10 gene transcription; promoted B7-1 and B7-2 gene transcription. E2 （50 ng/ml, pregnant level） inhibited the proliferation of the activated splenic cells; promoted CTLA-4, B7-1, IL-10 but inhibited B7-2 and TGF-β gene transcription. Therefore, we conclude that the effects of E2 on T cell activation are partially through its regulation on the co-stimulatory molecules. The co-stimulatory molecules are crucial components of the cell-contact dependent regulatory mechanism, and E2 may regulate T cell activation by this mechanism.
