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Full-Text Articles in Life Sciences
Multiple Specificities In The Murine Cd4+ And Cd8+ T-Cell Response To Dengue Virus, Alan Rothman, Ichiro Kurane, Francis Ennis
Multiple Specificities In The Murine Cd4+ And Cd8+ T-Cell Response To Dengue Virus, Alan Rothman, Ichiro Kurane, Francis Ennis
Alan Rothman
The target epitopes, serotype specificity, and cytolytic function of dengue virus-specific T cells may influence their theoretical roles in protection against secondary infection as well as the immunopathogenesis of dengue hemorrhagic fever. To study these factors in an experimental system, we isolated dengue virus-specific CD4+ and CD8+ T-cell clones from dengue-2 virus-immunized BALB/c mice. The T-cell response to dengue virus in this mouse strain was heterogeneous; we identified at least five different CD4+ phenotypes and six different CD8+ phenotypes. Individual T-cell clones recognized epitopes on the dengue virus pre-M, E, NSl/NS2A, and NS3 proteins and were restricted by the I-Ad, …
Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green
Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green
Alan Rothman
ChimeriVax-WN02 is a novel live-attenuated West Nile virus (WNV) vaccine containing modified WNV premembrane (prM) and envelope (E) sequences inserted into the yellow fever 17D vaccine genome. We investigated the induction and evolution of CD8(+) T cell responses to a WNV envelope epitope, which is a dominant target in naturally infected HLA-A*02-positive individuals. WNV epitope-specific CD8(+) T cells were detected by HLA tetramer staining in 22 of 23 donors tested, with peak frequencies occurring between days 14 and 28. WNV epitope-specific T cells evolved from an effector phenotype to a long-lived memory phenotype. In the majority of donors, CD8(+) T …
Cross-Reactive Memory Cd8(+) T Cells Alter The Immune Response To Heterologous Secondary Dengue Virus Infections In Mice In A Sequence-Specific Manner, Coreen Beaumier, Anuja Mathew, Hema Bashyam, Alan Rothman
Cross-Reactive Memory Cd8(+) T Cells Alter The Immune Response To Heterologous Secondary Dengue Virus Infections In Mice In A Sequence-Specific Manner, Coreen Beaumier, Anuja Mathew, Hema Bashyam, Alan Rothman
Alan Rothman
Dengue virus is the causative agent of dengue fever and the more-severe dengue hemorrhagic fever (DHF). Human studies suggest that the increased risk of DHF during secondary infection is due to immunopathology partially mediated by cross-reactive memory T cells from the primary infection. To model T cell responses to sequential infections, we immunized mice with different sequences of dengue virus serotypes and measured the frequency of peptide-specific T cells after infection. The acute response after heterologous secondary infections was enhanced compared with the acute or memory response after primary infection. Also, the hierarchy of epitope-specific responses was influenced by the …
Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman
Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman
Alan Rothman
We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA …
Dominant Recognition By Human Cd8+ Cytotoxic T Lymphocytes Of Dengue Virus Nonstructural Proteins Ns3 And Ns1.2a, Anuja Mathew, Ichiro Kurane, Alan Rothman, Lingling Zeng, Margo Brinton, Francis Ennis
Dominant Recognition By Human Cd8+ Cytotoxic T Lymphocytes Of Dengue Virus Nonstructural Proteins Ns3 And Ns1.2a, Anuja Mathew, Ichiro Kurane, Alan Rothman, Lingling Zeng, Margo Brinton, Francis Ennis
Alan Rothman
A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the …
Quantitation Of Cd8+ T Cell Responses To Newly Identified Hla-A*0201-Restricted T Cell Epitopes Conserved Among Vaccinia And Variola (Smallpox) Viruses, Masanori Terajima, John Cruz, Gregory Raines, Elizabeth Kilpatrick, Jeffrey Kennedy, Alan Rothman, Francis Ennis
Quantitation Of Cd8+ T Cell Responses To Newly Identified Hla-A*0201-Restricted T Cell Epitopes Conserved Among Vaccinia And Variola (Smallpox) Viruses, Masanori Terajima, John Cruz, Gregory Raines, Elizabeth Kilpatrick, Jeffrey Kennedy, Alan Rothman, Francis Ennis
Alan Rothman
Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in …
Dengue Virus-Reactive Cd8+ T Cells Display Quantitative And Qualitative Differences In Their Response To Variant Epitopes Of Heterologous Viral Serotypes, Hema Bashyam, Sharone Green, Alan Rothman
Dengue Virus-Reactive Cd8+ T Cells Display Quantitative And Qualitative Differences In Their Response To Variant Epitopes Of Heterologous Viral Serotypes, Hema Bashyam, Sharone Green, Alan Rothman
Alan Rothman
Reactivation of serotype cross-reactive CD8+ memory T lymphocytes is thought to contribute to the immunopathogenesis of dengue disease during secondary infection by a heterologous serotype. Using cytokine flow cytometry, we have defined four novel HLA-A*02-restricted dengue viral epitopes recognized by up to 1.5% of circulating CD8+ T cells in four donors after primary vaccination. All four donors had the highest cytokine response to the epitope NS4b 2353. We also studied the effect of sequence differences in heterologous dengue serotypes on dengue-reactive CD8+ memory T cell cytokine and proliferative responses. The D3 variant of a different NS4b epitope 2423 and the …
Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green
Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green
Sharone Green
ChimeriVax-WN02 is a novel live-attenuated West Nile virus (WNV) vaccine containing modified WNV premembrane (prM) and envelope (E) sequences inserted into the yellow fever 17D vaccine genome. We investigated the induction and evolution of CD8(+) T cell responses to a WNV envelope epitope, which is a dominant target in naturally infected HLA-A*02-positive individuals. WNV epitope-specific CD8(+) T cells were detected by HLA tetramer staining in 22 of 23 donors tested, with peak frequencies occurring between days 14 and 28. WNV epitope-specific T cells evolved from an effector phenotype to a long-lived memory phenotype. In the majority of donors, CD8(+) T …
Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman
Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman
Sharone Green
We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA …
Dengue Virus-Reactive Cd8+ T Cells Display Quantitative And Qualitative Differences In Their Response To Variant Epitopes Of Heterologous Viral Serotypes, Hema Bashyam, Sharone Green, Alan Rothman
Dengue Virus-Reactive Cd8+ T Cells Display Quantitative And Qualitative Differences In Their Response To Variant Epitopes Of Heterologous Viral Serotypes, Hema Bashyam, Sharone Green, Alan Rothman
Sharone Green
Reactivation of serotype cross-reactive CD8+ memory T lymphocytes is thought to contribute to the immunopathogenesis of dengue disease during secondary infection by a heterologous serotype. Using cytokine flow cytometry, we have defined four novel HLA-A*02-restricted dengue viral epitopes recognized by up to 1.5% of circulating CD8+ T cells in four donors after primary vaccination. All four donors had the highest cytokine response to the epitope NS4b 2353. We also studied the effect of sequence differences in heterologous dengue serotypes on dengue-reactive CD8+ memory T cell cytokine and proliferative responses. The D3 variant of a different NS4b epitope 2423 and the …
Long Term Recall Of Memory Cd8 T Cells In Mice To First And Third Generation Smallpox Vaccines, Sharone Green, Francis Ennis, Anuja Mathew
Long Term Recall Of Memory Cd8 T Cells In Mice To First And Third Generation Smallpox Vaccines, Sharone Green, Francis Ennis, Anuja Mathew
Sharone Green
Since long-term immunity is a critical component of any effective vaccine, we compared over a 15-month period, the strength, durability and specificity of immunity of an attenuated smallpox vaccine Modified Vaccinia Ankara (MVA) to the New York City Board of Health (NYCBH) vaccine. The frequencies of CD8(+) T cells to an immunodominant CD8 T cell epitope B8R(20-27) remained remarkably stable in mice given either MVA or NYCBH. Both groups were also protected from a lethal intranasal challenge with Western Reserve strain of vaccinia virus (VACV-WR). Cytokine responses to virus-specific peptides were detectable with significant boosting upon challenge. Expression of most …
Altered Effector Functions Of Virus-Specific And Virus Cross-Reactive Cd8+ T Cells In Mice Immunized With Related Flaviviruses., Derek Trobaugh, Liyan Yang, Francis Ennis, Sharone Green
Altered Effector Functions Of Virus-Specific And Virus Cross-Reactive Cd8+ T Cells In Mice Immunized With Related Flaviviruses., Derek Trobaugh, Liyan Yang, Francis Ennis, Sharone Green
Sharone Green
Memory cross-reactive CD8+ T-cell responses may induce protection or immunopathology upon secondary viral challenge. To elucidate the potential role of T cells in sequential flavivirus infection, we characterized cross-reactive CD4+ and CD8+ T-cell responses between attenuated and pathogenic Japanese encephalitis virus (JEV) and pathogenic West Nile virus (WNV). A previously reported WNV NS4b CD8+ T-cell epitope and its JEV variant elicited CD8+ T-cell responses in both JEV- and WNV-infected mice. The peptide variant homologous to the immunizing virus induced greater cytokine secretion and activated higher frequencies of epitope-specific CD8+ T cells. However, there was a virus-dependent, peptide variant-independent pattern of …