Temporal dynamics of the primary human T cell response to yellow fever virus 17D as it matures from an effector- to a memory-type response
The live attenuated yellow fever virus (YFV) 17D vaccine provides a good model to study immune responses to an acute viral infection in humans. We studied the temporal dynamics, composition, and character of the primary human T cell response to YFV. The acute YFV-specific effector CD8 T cell respons...
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| Vydáno v: | The Journal of immunology (1950) Ročník 190; číslo 5; s. 2150 |
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| Hlavní autoři: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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United States
01.03.2013
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| ISSN: | 1550-6606, 1550-6606 |
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| Abstract | The live attenuated yellow fever virus (YFV) 17D vaccine provides a good model to study immune responses to an acute viral infection in humans. We studied the temporal dynamics, composition, and character of the primary human T cell response to YFV. The acute YFV-specific effector CD8 T cell response was broad and complex; it was composed of dominant responses that persisted into the memory population, as well as of transient subdominant responses that were not detected at the memory stage. Furthermore, HLA-A2- and HLA-B7-restricted YFV epitope-specific effector cells predominantly displayed a CD45RA(-)CCR7(-)PD-1(+)CD27(high) phenotype, which transitioned into a CD45RA(+)CCR7(-)PD-1(-)CD27(low) memory population phenotype. The functional profile of the YFV-specific CD8 T cell response changed in composition as it matured from an effector- to a memory-type response, and it tended to become less polyfunctional during the course of this transition. Interestingly, activation of CD4 T cells, as well as FOXP3(+) T regulatory cells, in response to YFV vaccination preceded the kinetics of the CD8 T cell response. The present results contribute to our understanding of how immunodominance patterns develop, as well as the phenotypic and functional characteristics of the primary human T cell response to a viral infection as it evolves and matures into memory. |
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| AbstractList | The live attenuated yellow fever virus (YFV) 17D vaccine provides a good model to study immune responses to an acute viral infection in humans. We studied the temporal dynamics, composition, and character of the primary human T cell response to YFV. The acute YFV-specific effector CD8 T cell response was broad and complex; it was composed of dominant responses that persisted into the memory population, as well as of transient subdominant responses that were not detected at the memory stage. Furthermore, HLA-A2- and HLA-B7-restricted YFV epitope-specific effector cells predominantly displayed a CD45RA(-)CCR7(-)PD-1(+)CD27(high) phenotype, which transitioned into a CD45RA(+)CCR7(-)PD-1(-)CD27(low) memory population phenotype. The functional profile of the YFV-specific CD8 T cell response changed in composition as it matured from an effector- to a memory-type response, and it tended to become less polyfunctional during the course of this transition. Interestingly, activation of CD4 T cells, as well as FOXP3(+) T regulatory cells, in response to YFV vaccination preceded the kinetics of the CD8 T cell response. The present results contribute to our understanding of how immunodominance patterns develop, as well as the phenotypic and functional characteristics of the primary human T cell response to a viral infection as it evolves and matures into memory.The live attenuated yellow fever virus (YFV) 17D vaccine provides a good model to study immune responses to an acute viral infection in humans. We studied the temporal dynamics, composition, and character of the primary human T cell response to YFV. The acute YFV-specific effector CD8 T cell response was broad and complex; it was composed of dominant responses that persisted into the memory population, as well as of transient subdominant responses that were not detected at the memory stage. Furthermore, HLA-A2- and HLA-B7-restricted YFV epitope-specific effector cells predominantly displayed a CD45RA(-)CCR7(-)PD-1(+)CD27(high) phenotype, which transitioned into a CD45RA(+)CCR7(-)PD-1(-)CD27(low) memory population phenotype. The functional profile of the YFV-specific CD8 T cell response changed in composition as it matured from an effector- to a memory-type response, and it tended to become less polyfunctional during the course of this transition. Interestingly, activation of CD4 T cells, as well as FOXP3(+) T regulatory cells, in response to YFV vaccination preceded the kinetics of the CD8 T cell response. The present results contribute to our understanding of how immunodominance patterns develop, as well as the phenotypic and functional characteristics of the primary human T cell response to a viral infection as it evolves and matures into memory. The live attenuated yellow fever virus (YFV) 17D vaccine provides a good model to study immune responses to an acute viral infection in humans. We studied the temporal dynamics, composition, and character of the primary human T cell response to YFV. The acute YFV-specific effector CD8 T cell response was broad and complex; it was composed of dominant responses that persisted into the memory population, as well as of transient subdominant responses that were not detected at the memory stage. Furthermore, HLA-A2- and HLA-B7-restricted YFV epitope-specific effector cells predominantly displayed a CD45RA(-)CCR7(-)PD-1(+)CD27(high) phenotype, which transitioned into a CD45RA(+)CCR7(-)PD-1(-)CD27(low) memory population phenotype. The functional profile of the YFV-specific CD8 T cell response changed in composition as it matured from an effector- to a memory-type response, and it tended to become less polyfunctional during the course of this transition. Interestingly, activation of CD4 T cells, as well as FOXP3(+) T regulatory cells, in response to YFV vaccination preceded the kinetics of the CD8 T cell response. The present results contribute to our understanding of how immunodominance patterns develop, as well as the phenotypic and functional characteristics of the primary human T cell response to a viral infection as it evolves and matures into memory. |
| Author | Blom, Kim Braun, Monika Falconer, Karolin Ljunggren, Hans-Gustaf Michaëlsson, Jakob Ivarsson, Martin A Sandberg, Johan K Gonzalez, Veronica D Moll, Markus |
| Author_xml | – sequence: 1 givenname: Kim surname: Blom fullname: Blom, Kim organization: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden – sequence: 2 givenname: Monika surname: Braun fullname: Braun, Monika – sequence: 3 givenname: Martin A surname: Ivarsson fullname: Ivarsson, Martin A – sequence: 4 givenname: Veronica D surname: Gonzalez fullname: Gonzalez, Veronica D – sequence: 5 givenname: Karolin surname: Falconer fullname: Falconer, Karolin – sequence: 6 givenname: Markus surname: Moll fullname: Moll, Markus – sequence: 7 givenname: Hans-Gustaf surname: Ljunggren fullname: Ljunggren, Hans-Gustaf – sequence: 8 givenname: Jakob surname: Michaëlsson fullname: Michaëlsson, Jakob – sequence: 9 givenname: Johan K surname: Sandberg fullname: Sandberg, Johan K |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23338234$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Adolescent Adult CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - pathology CD4-Positive T-Lymphocytes - virology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology CD8-Positive T-Lymphocytes - virology Cytokines - biosynthesis Cytokines - immunology Histocompatibility Testing HLA Antigens - genetics HLA Antigens - immunology Humans Immunologic Memory Immunophenotyping Middle Aged Time Factors Vaccines, Attenuated - administration & dosage Vaccines, Attenuated - immunology Yellow Fever - immunology Yellow Fever - pathology Yellow Fever - prevention & control Yellow Fever - virology Yellow Fever Vaccine - administration & dosage Yellow Fever Vaccine - immunology Yellow fever virus - immunology |
| Title | Temporal dynamics of the primary human T cell response to yellow fever virus 17D as it matures from an effector- to a memory-type response |
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