CD4＋ helper T （Th） cells play pivotal roles in induction of CD8＋ CTL immunity. However, the mechanism of CD4＋ T cell help delivery to CD8＋ T cells in vivo is still elusive. In this study, we used ovalbumin （OVA...CD4＋ helper T （Th） cells play pivotal roles in induction of CD8＋ CTL immunity. However, the mechanism of CD4＋ T cell help delivery to CD8＋ T cells in vivo is still elusive. In this study, we used ovalbumin （OVA）-pulsed dendritic cells （DCovA） to activate OT-II mouse CD4＋ T cells, and then studied the help effect of these CD4＋ T cells on CD8＋ cytotoxic T lymphocyte （CTL） responses＋ We also examined CTL mediated islet β cell destruction which leaded to diabetes in wild-type C57BL/6 mice and transgenic rat insulin promoter （RIP）-mOVA mice expressing β cell antigen OVA with self OVA-specific tolerance, respectively. In adoptive transfer experiments, we demonstrated that help, in the form of peptide/major histocompatibility complex （pMHC） I acquired from DCovA by DCovA activation, was required for induction of OVA-specific CTL responses in C57BL/6 mice. However, in combination ＋ ＋ ＋ with TCR transgenlc OT-I mouse CD8 T ceils, the tolerogenic dosage of CD4＋ Th cells with acquired pMHC I, but not CD4＋ （Kb-/-） Th cells without acquired pMHC I were able to cause diabetes in 8/10 （80%） RIP-mOVA mice. This study thus expands the current knowledge in T cell-mediated autoimmunity and provides insight into the nature of CD4＋ T cell-mediated help in CD8＋ CTL induction. Cellular ＆ Molecular Immunology. 2008;5（6）：407-415.展开更多
Autoimmune diseases are generated through irregular immune response of the human body. Psoriasis is one type of autoimmune chronic skin diseases that is differentiated by T-Cells mediated hyper-proliferation of epider...Autoimmune diseases are generated through irregular immune response of the human body. Psoriasis is one type of autoimmune chronic skin diseases that is differentiated by T-Cells mediated hyper-proliferation of epidermal Keratinocytes. Dendritic Cells and CD8＋ T-Cells have a significant role for the occurrence of this disease. In this paper, the authors have developed a mathematical model of Psoriasis involving CD4＋ T-Cells, Dendritic Ceils, CD8＋ T-Cells and Keratinocyte cell populations using the fractional differential equations with the effect of Cytokine release to observe the impact of memory on the cell-biological system. Using fractional calculus, the authors try to explore the suppressed memory, associated with the cell-biological system and to locate the position of Keratinocyte cell population as fractional derivative possess non-local property. Thus, the dynamics of Psoriasis can be predicted in a better way using fractional differential equations rather than its corresponding integer order model. Finally, the authors introduce drug into the system to obstruct the interaction between CD4＋ T-Cells and Keratinocytes to restrict the disease Psoriasis. The authors derive the Euler-Lagrange conditions for the optimality made through Matlab by developing iterative of the drug induced system. Numerical simulations are schemes.展开更多
基金supported by research funds from Canadian Institute of Health Research (MOP 79415, 81228 and 89713)
文摘CD4＋ helper T （Th） cells play pivotal roles in induction of CD8＋ CTL immunity. However, the mechanism of CD4＋ T cell help delivery to CD8＋ T cells in vivo is still elusive. In this study, we used ovalbumin （OVA）-pulsed dendritic cells （DCovA） to activate OT-II mouse CD4＋ T cells, and then studied the help effect of these CD4＋ T cells on CD8＋ cytotoxic T lymphocyte （CTL） responses＋ We also examined CTL mediated islet β cell destruction which leaded to diabetes in wild-type C57BL/6 mice and transgenic rat insulin promoter （RIP）-mOVA mice expressing β cell antigen OVA with self OVA-specific tolerance, respectively. In adoptive transfer experiments, we demonstrated that help, in the form of peptide/major histocompatibility complex （pMHC） I acquired from DCovA by DCovA activation, was required for induction of OVA-specific CTL responses in C57BL/6 mice. However, in combination ＋ ＋ ＋ with TCR transgenlc OT-I mouse CD8 T ceils, the tolerogenic dosage of CD4＋ Th cells with acquired pMHC I, but not CD4＋ （Kb-/-） Th cells without acquired pMHC I were able to cause diabetes in 8/10 （80%） RIP-mOVA mice. This study thus expands the current knowledge in T cell-mediated autoimmunity and provides insight into the nature of CD4＋ T cell-mediated help in CD8＋ CTL induction. Cellular ＆ Molecular Immunology. 2008;5（6）：407-415.
基金supported by the Council of Scientific and Industrial Research,Government of India under Grant No.38(1320)/12/EMR-II
文摘Autoimmune diseases are generated through irregular immune response of the human body. Psoriasis is one type of autoimmune chronic skin diseases that is differentiated by T-Cells mediated hyper-proliferation of epidermal Keratinocytes. Dendritic Cells and CD8＋ T-Cells have a significant role for the occurrence of this disease. In this paper, the authors have developed a mathematical model of Psoriasis involving CD4＋ T-Cells, Dendritic Ceils, CD8＋ T-Cells and Keratinocyte cell populations using the fractional differential equations with the effect of Cytokine release to observe the impact of memory on the cell-biological system. Using fractional calculus, the authors try to explore the suppressed memory, associated with the cell-biological system and to locate the position of Keratinocyte cell population as fractional derivative possess non-local property. Thus, the dynamics of Psoriasis can be predicted in a better way using fractional differential equations rather than its corresponding integer order model. Finally, the authors introduce drug into the system to obstruct the interaction between CD4＋ T-Cells and Keratinocytes to restrict the disease Psoriasis. The authors derive the Euler-Lagrange conditions for the optimality made through Matlab by developing iterative of the drug induced system. Numerical simulations are schemes.
