In this paper, a mathematical model for HTLV-I infection of CD4＋ T cells that incorporates the CD8＋ cytotoxic T-cell（CTL） response is studied. We establish two threshold parameters Ro and R1, the basic reproductio...In this paper, a mathematical model for HTLV-I infection of CD4＋ T cells that incorporates the CD8＋ cytotoxic T-cell（CTL） response is studied. We establish two threshold parameters Ro and R1, the basic reproduction numbers for viral persistence and for CTL response, respectively. We also show that the parameter R1 can be used to distinguish asymptomatic carriers from HAM/TSP patients and as an important control parameter for preventing the development of HAM/TSP.展开更多
Radiofrequency ablation(RFA)is the most common approach to thermal ablation for cancer therapy.Unfortunately,its efficacy is limited by incomplete ablation,and further optimization of RFA is required.Here,we demonstra...Radiofrequency ablation(RFA)is the most common approach to thermal ablation for cancer therapy.Unfortunately,its efficacy is limited by incomplete ablation,and further optimization of RFA is required.Here,we demonstrate that incubation at 65°C triggers more EG7 tumor cell death by necrosis than treatment at 45°C,and the 65°C-treated cells are more effective at inducing antigen-specific CD8^(+)cytotoxic T lymphocyte(CTL)responses after injection in mice than the 45°C-treated ones.Dendritic cells(DCs)that phagocytose 65°C-treated EG7 cells become mature with upregulated MHCII and CD80 expression and are capable of efficiently inducing effector CTLs in mouse tumor models.RFA(65°C)therapy of EG7 tumors induces large areas of tumor necrosis and stimulates CTL responses.This leads to complete regression of small(~100 mm^(3))tumors but fails to suppress the growth of larger(~350 mm^(3))tumors.The administration of the Toll-like receptor-9(TLR9)agonist unmethylated cytosine-phosphorothioate-guanine oligonucleotide(CpG)to DCs phagocytosing 65°C-treated EG7 cells enhances the expression of MHCII and CD40 on DCs as well as DC-induced stimulation of CTL responses.Importantly,the intratumoral administration of CpG following RFA also increases the frequencies of tumor-associated immunogenic CD11b−CD11c^(+)CD103^(+)DC2 and CD11b+F4/80+MHCII+M1 macrophages and increases CD4^(+)and CD8^(+)T-cell tumor infiltration,leading to enhanced CD4^(+)T cell-dependent CTL responses and potent inhibition of primary RFA-treated or distant untreated tumor growth as well as tumor lung metastasis in mice bearing larger tumors.Overall,our data indicate that CpG administration,which enhances RFA-induced CTL responses and ultimately potentiates the inhibition of primary tumor growth and lung metastasis,is a promising strategy for improving RFA treatment,which may assist in optimizing this important cancer therapy.展开更多
It is beyond dispute that cytotoxic T-lymphocytes(CTLs)exert a vital function in the host's antiviral defense mechanism.With the idea of the above factor and the logistic proliferation of CD4+T-cells,we establish ...It is beyond dispute that cytotoxic T-lymphocytes(CTLs)exert a vital function in the host's antiviral defense mechanism.With the idea of the above factor and the logistic proliferation of CD4+T-cells,we establish a HTLV-I(human T-cell leukemia virus type-I)mathematical model.First,two threshold parameters Ro and Re(the basic reproduction numbers for viral infection and CTL immune response,respectively)are obtained.Second,sufficient criteria for local and global asymptotic stabilities of the feasible equilibria of the model are deduced,respectively.Third,the sensitivity analyses of Ro and Rc are performed to better understand the effective strategies for HTLV-I infection.Finally,not only numerical simulations are given to illustrate the stability conclusions,but also the biological significance is stated.展开更多
This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical ...This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained. Global stability of the positive equilibrium of the model is also considered. The results show that the free diffusion of the virus has no effect on the global stability of such HBV infection problem with Neumann homogeneous boundary conditions.展开更多
In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free viru...In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.展开更多
In this paper, a virus infection model with standard incidence rate and delayed CTL immune response is investigated. By analyzing corresponding characteristic equations,the local stability of each of feasible equilibr...In this paper, a virus infection model with standard incidence rate and delayed CTL immune response is investigated. By analyzing corresponding characteristic equations,the local stability of each of feasible equilibria and the existence of Hopf bifurcations at the CTL-activated infection equilibrium are established, respectively. By means of comparison arguments, it is verified that the infection-free equilibrium is globally asymptotically stable if the basic reproduction ratio is less than unity. By using suitable Lyapunov functional and LaSalle's invariance principle, it is shown that the CTL-inactivated infection equilibrium of the system is globally asymptotically stable if the immune response reproduction ratio is less than unity and the basic reproduction ratio is greater than unity. Numerical simulations are carried out to illustrate the theoretical result.展开更多
In this work, we investigate an HIV-1 infection model with a general incidence rate and delayed CTL immune response. The model admits three possible equilibria, an infection-free equilibrium E<sup>*</sup>&...In this work, we investigate an HIV-1 infection model with a general incidence rate and delayed CTL immune response. The model admits three possible equilibria, an infection-free equilibrium E<sup>*</sup><sub style="margin-left:-6px;">0</sub>, CTL-inactivated infection equilibrium E<sup>*</sup><sub style="margin-left:-6px;">1</sub> and CTL-activated infection equilibrium E<sup>*</sup><sub style="margin-left:-6px;">2</sub>. We prove that in the absence of CTL immune delay, the model has exactly the basic behaviour model, for all positive intracellular delays, the global dynamics are determined by two threshold parameters R<sub>0</sub> and R<sub>1</sub>, if R<sub>0</sub> <span style="font-size:12px;white-space:nowrap;">≤ 1, E<sup>*</sup><span style="margin-left:-6px;"><sub>0</sub> is globally asymptotically stable, if R<sub>1</sub> <span style="font-size:12px;white-space:nowrap;">≤ 1 < R<sub>0</sub>, E<sup>*</sup><span style="margin-left:-6px;"><sub>1</sub> is globally asymptotically stable and if R<sub>1</sub> >1, E<sup>*</sup><span style="margin-left:-6px;"><sub>2</sub> is globally asymptotically stable. But if the CTL immune response delay is different from zero, then the behaviour of the model at E<sup>*</sup><span style="margin-left:-6px;"><sub>2</sub> changes completely, although R<sub>1</sub> > 1, a Hopf bifurcation at E<sup>*</sup><span style="margin-left:-6px;"><sub>2</sub> is established. In the end, we present some numerical simulations.展开更多
This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive soluti...This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.展开更多
In this paper, we study a fractional-order model with time-delay to describe the dynamics of Ebola virus infection with cytotoxic T-lymphocyte （CTL） response in vivo. The time- delay is introduced in the CTL respons...In this paper, we study a fractional-order model with time-delay to describe the dynamics of Ebola virus infection with cytotoxic T-lymphocyte （CTL） response in vivo. The time- delay is introduced in the CTL response term to represent time required to stimulate the immune system. Based on fractional Laplace transform, some conditions on stability and Hopf bifurcation are derived for the model. The analysis shows that the fractional- order with time-delay can effectively enrich the dynamics and strengthen the stability condition of fractional-order infection model. Finally, the derived theoretical results are justified by some numerical simulations.展开更多
This paper studies the dynamical behavior of an HIV-1 infection model with satu- rated virus-target and infected-target incidences with Cytotoxic T Lymphocyte （CTL） immune response. The model is incorporated by two ...This paper studies the dynamical behavior of an HIV-1 infection model with satu- rated virus-target and infected-target incidences with Cytotoxic T Lymphocyte （CTL） immune response. The model is incorporated by two types of intracellular distributed time delays. The model generalizes all the existing HIV-1 infection models with cell-to- cell transmission presented in the literature by considering saturated incidence rate and the effect of CTL immune response. The existence and global stability of all steady states of the model are determined by two parameters, the basic reproduction number （R0） and the CTL immune response activation number （R1）. By using suitable Lyapunov functionals, we show that if R0≤1, then the infection-free steady state So is globally asymptotically stable; if R1≤1〈R0, then the CTL-inactivated infection steady state S1 is globally asymptotically stable; if R1〉1, then the CTL-activated infection steady state S2 is globally asymptotically stable. Using MATLAB we conduct some numerical simulations to confirm our results. The effect of the saturated incidence of the HIV-1 dynamics is shown.展开更多
Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhanc...Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular ＆ Molecular Immunology. 2008;5（4）：261-269.展开更多
In this paper, a HTLV-I infection model with two delays is considered. It is found that the dynamics of this model are determined by two threshold parameters R0 and R1, basic reproduction numbers for viral infection a...In this paper, a HTLV-I infection model with two delays is considered. It is found that the dynamics of this model are determined by two threshold parameters R0 and R1, basic reproduction numbers for viral infection and for CTL response, respectively. If R0 〈 1, the infection-free equilibrium P0 is globally asymptotically stable. If R1 〈 1 〈 R0, the asymptomatic-carrier equilibrium P1 is globally asymptotically stable. If R1 〉 1, there exists a unique HAM/TSP equilibrium P2. The stability of P2 is changed when the second delay T2 varies, that is there exist stability switches for P2.展开更多
基金Supported by the Scientic and Technological Project of Henan Province(122300410034,132300410344)Supported by the the Universities Young Teachers Program of Henan Province(2010GGJS-104)
文摘In this paper, a mathematical model for HTLV-I infection of CD4＋ T cells that incorporates the CD8＋ cytotoxic T-cell（CTL） response is studied. We establish two threshold parameters Ro and R1, the basic reproduction numbers for viral persistence and for CTL response, respectively. We also show that the parameter R1 can be used to distinguish asymptomatic carriers from HAM/TSP patients and as an important control parameter for preventing the development of HAM/TSP.
基金supported by grants from CoMRAD(#417578)College of Medicine,University of Saskatchewan,Prostate Cancer Fight Foundation(#417782)+1 种基金Royal University Hospital Research Foundation(#417450)Saskatchewan Health Research Foundation(#418672).
文摘Radiofrequency ablation(RFA)is the most common approach to thermal ablation for cancer therapy.Unfortunately,its efficacy is limited by incomplete ablation,and further optimization of RFA is required.Here,we demonstrate that incubation at 65°C triggers more EG7 tumor cell death by necrosis than treatment at 45°C,and the 65°C-treated cells are more effective at inducing antigen-specific CD8^(+)cytotoxic T lymphocyte(CTL)responses after injection in mice than the 45°C-treated ones.Dendritic cells(DCs)that phagocytose 65°C-treated EG7 cells become mature with upregulated MHCII and CD80 expression and are capable of efficiently inducing effector CTLs in mouse tumor models.RFA(65°C)therapy of EG7 tumors induces large areas of tumor necrosis and stimulates CTL responses.This leads to complete regression of small(~100 mm^(3))tumors but fails to suppress the growth of larger(~350 mm^(3))tumors.The administration of the Toll-like receptor-9(TLR9)agonist unmethylated cytosine-phosphorothioate-guanine oligonucleotide(CpG)to DCs phagocytosing 65°C-treated EG7 cells enhances the expression of MHCII and CD40 on DCs as well as DC-induced stimulation of CTL responses.Importantly,the intratumoral administration of CpG following RFA also increases the frequencies of tumor-associated immunogenic CD11b−CD11c^(+)CD103^(+)DC2 and CD11b+F4/80+MHCII+M1 macrophages and increases CD4^(+)and CD8^(+)T-cell tumor infiltration,leading to enhanced CD4^(+)T cell-dependent CTL responses and potent inhibition of primary RFA-treated or distant untreated tumor growth as well as tumor lung metastasis in mice bearing larger tumors.Overall,our data indicate that CpG administration,which enhances RFA-induced CTL responses and ultimately potentiates the inhibition of primary tumor growth and lung metastasis,is a promising strategy for improving RFA treatment,which may assist in optimizing this important cancer therapy.
基金supported by the National Natural Science Foundation(NNSF)of China(Nos.11871201,11871238 and 12001178)。
文摘It is beyond dispute that cytotoxic T-lymphocytes(CTLs)exert a vital function in the host's antiviral defense mechanism.With the idea of the above factor and the logistic proliferation of CD4+T-cells,we establish a HTLV-I(human T-cell leukemia virus type-I)mathematical model.First,two threshold parameters Ro and Re(the basic reproduction numbers for viral infection and CTL immune response,respectively)are obtained.Second,sufficient criteria for local and global asymptotic stabilities of the feasible equilibria of the model are deduced,respectively.Third,the sensitivity analyses of Ro and Rc are performed to better understand the effective strategies for HTLV-I infection.Finally,not only numerical simulations are given to illustrate the stability conclusions,but also the biological significance is stated.
基金supported by the National Natural Science Foundation of China(10971166,10901131)the National High Technology Research and Development Program of China(863 Program,2009AA01A135)the Natural Science Foundation of Xinjiang Province(2010211B04)
文摘This article proposes a diffused hepatitis B virus （HBV） model with CTL immune response and nonlinear incidence for the control of viral infections. By means of different Lyapunov functions, the global asymptotical properties of the viral-free equilibrium and immune-free equilibrium of the model are obtained. Global stability of the positive equilibrium of the model is also considered. The results show that the free diffusion of the virus has no effect on the global stability of such HBV infection problem with Neumann homogeneous boundary conditions.
基金The work was supported by NSF of China(11201002)Natural Science Foundation of Universities in Anhui Province(KJ2017A815).
文摘In this paper,dynamics analysis of a delayed HIV infection model with CTL immune response and antibody immune response is investigated.The model involves the concentrations of uninfected cells,infected cells,free virus,CTL response cells,and antibody antibody response cells.There are three delays in the model:the intracellular delay,virus replication delay and the antibody delay.The basic reproductive number of viral infection,the antibody immune reproductive number,the CTL immune reproductive number,the CTL immune competitive reproductive number and the antibody immune competitive reproductive number are derived.By means of Lyapunov functionals and LaSalle’s invariance principle,sufficient conditions for the stability of each equilibrium is established.The results show that the intracellular delay and virus replication delay do not impact upon the stability of each equilibrium,but when the antibody delay is positive,Hopf bifurcation at the antibody response and the interior equilibrium will exist by using the antibody delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.
基金Supported by the NNSF of China(11371368,11071254)Supported by the NSF of Hebei Province(A2014506015)Supported by the NSF for Young Scientists of Hebei Province(A2013506012)
文摘In this paper, a virus infection model with standard incidence rate and delayed CTL immune response is investigated. By analyzing corresponding characteristic equations,the local stability of each of feasible equilibria and the existence of Hopf bifurcations at the CTL-activated infection equilibrium are established, respectively. By means of comparison arguments, it is verified that the infection-free equilibrium is globally asymptotically stable if the basic reproduction ratio is less than unity. By using suitable Lyapunov functional and LaSalle's invariance principle, it is shown that the CTL-inactivated infection equilibrium of the system is globally asymptotically stable if the immune response reproduction ratio is less than unity and the basic reproduction ratio is greater than unity. Numerical simulations are carried out to illustrate the theoretical result.
文摘In this work, we investigate an HIV-1 infection model with a general incidence rate and delayed CTL immune response. The model admits three possible equilibria, an infection-free equilibrium E<sup>*</sup><sub style="margin-left:-6px;">0</sub>, CTL-inactivated infection equilibrium E<sup>*</sup><sub style="margin-left:-6px;">1</sub> and CTL-activated infection equilibrium E<sup>*</sup><sub style="margin-left:-6px;">2</sub>. We prove that in the absence of CTL immune delay, the model has exactly the basic behaviour model, for all positive intracellular delays, the global dynamics are determined by two threshold parameters R<sub>0</sub> and R<sub>1</sub>, if R<sub>0</sub> <span style="font-size:12px;white-space:nowrap;">≤ 1, E<sup>*</sup><span style="margin-left:-6px;"><sub>0</sub> is globally asymptotically stable, if R<sub>1</sub> <span style="font-size:12px;white-space:nowrap;">≤ 1 < R<sub>0</sub>, E<sup>*</sup><span style="margin-left:-6px;"><sub>1</sub> is globally asymptotically stable and if R<sub>1</sub> >1, E<sup>*</sup><span style="margin-left:-6px;"><sub>2</sub> is globally asymptotically stable. But if the CTL immune response delay is different from zero, then the behaviour of the model at E<sup>*</sup><span style="margin-left:-6px;"><sub>2</sub> changes completely, although R<sub>1</sub> > 1, a Hopf bifurcation at E<sup>*</sup><span style="margin-left:-6px;"><sub>2</sub> is established. In the end, we present some numerical simulations.
文摘This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4<sup>+</sup> T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.
文摘In this paper, we study a fractional-order model with time-delay to describe the dynamics of Ebola virus infection with cytotoxic T-lymphocyte （CTL） response in vivo. The time- delay is introduced in the CTL response term to represent time required to stimulate the immune system. Based on fractional Laplace transform, some conditions on stability and Hopf bifurcation are derived for the model. The analysis shows that the fractional- order with time-delay can effectively enrich the dynamics and strengthen the stability condition of fractional-order infection model. Finally, the derived theoretical results are justified by some numerical simulations.
文摘This paper studies the dynamical behavior of an HIV-1 infection model with satu- rated virus-target and infected-target incidences with Cytotoxic T Lymphocyte （CTL） immune response. The model is incorporated by two types of intracellular distributed time delays. The model generalizes all the existing HIV-1 infection models with cell-to- cell transmission presented in the literature by considering saturated incidence rate and the effect of CTL immune response. The existence and global stability of all steady states of the model are determined by two parameters, the basic reproduction number （R0） and the CTL immune response activation number （R1）. By using suitable Lyapunov functionals, we show that if R0≤1, then the infection-free steady state So is globally asymptotically stable; if R1≤1〈R0, then the CTL-inactivated infection steady state S1 is globally asymptotically stable; if R1〉1, then the CTL-activated infection steady state S2 is globally asymptotically stable. Using MATLAB we conduct some numerical simulations to confirm our results. The effect of the saturated incidence of the HIV-1 dynamics is shown.
文摘Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular ＆ Molecular Immunology. 2008;5（4）：261-269.
基金Acknowledgments The authors would like to thank the reviewers＇ constructive suggestions which have improved the presentation of the paper. This research is supported by National Natural Science Foundation of China （No. 11371111）, the Research Fund for the Doctoral Program of Higher Education of China （No. 20122302110044） and Shandong Provincial Natural Science Foundation, China （No. ZR2013AQ023）.
文摘In this paper, a HTLV-I infection model with two delays is considered. It is found that the dynamics of this model are determined by two threshold parameters R0 and R1, basic reproduction numbers for viral infection and for CTL response, respectively. If R0 〈 1, the infection-free equilibrium P0 is globally asymptotically stable. If R1 〈 1 〈 R0, the asymptomatic-carrier equilibrium P1 is globally asymptotically stable. If R1 〉 1, there exists a unique HAM/TSP equilibrium P2. The stability of P2 is changed when the second delay T2 varies, that is there exist stability switches for P2.
