Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection.
<h4>Background</h4> <p>Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood.</p> <h...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2015
|
| _version_ | 1797084354912976896 |
|---|---|
| author | Jeewandara, C Adikari, T Gomes, L Fernando, S Fernando, R Perera, M Ariyaratne, D Kamaladasa, A Salimi, M Prathapan, S Ogg, G Malavige, G |
| author_facet | Jeewandara, C Adikari, T Gomes, L Fernando, S Fernando, R Perera, M Ariyaratne, D Kamaladasa, A Salimi, M Prathapan, S Ogg, G Malavige, G |
| author_sort | Jeewandara, C |
| collection | OXFORD |
| description | <h4>Background</h4> <p>Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood.</p> <h4>Methodology/Principal Findings</h4> <p>Using ex vivo IFNγELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFαand IFNγ(p=0.03) or TNFαalone.</p> <br/> <p>We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus.</p> <h4>Conclusions/Significance</h4> <p>The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials.</p> |
| first_indexed | 2024-03-07T01:54:20Z |
| format | Journal article |
| id | oxford-uuid:9b30e993-6a6a-4754-97a1-272f644058c2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:54:20Z |
| publishDate | 2015 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:9b30e993-6a6a-4754-97a1-272f644058c22022-03-27T00:27:02ZFunctionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9b30e993-6a6a-4754-97a1-272f644058c2EnglishSymplectic Elements at OxfordPublic Library of Science2015Jeewandara, CAdikari, TGomes, LFernando, SFernando, RPerera, MAriyaratne, DKamaladasa, ASalimi, MPrathapan, SOgg, GMalavige, G<h4>Background</h4> <p>Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood.</p> <h4>Methodology/Principal Findings</h4> <p>Using ex vivo IFNγELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFαand IFNγ(p=0.03) or TNFαalone.</p> <br/> <p>We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus.</p> <h4>Conclusions/Significance</h4> <p>The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials.</p> |
| spellingShingle | Jeewandara, C Adikari, T Gomes, L Fernando, S Fernando, R Perera, M Ariyaratne, D Kamaladasa, A Salimi, M Prathapan, S Ogg, G Malavige, G Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection. |
| title | Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection. |
| title_full | Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection. |
| title_fullStr | Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection. |
| title_full_unstemmed | Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection. |
| title_short | Functionality of dengue virus specific memory T cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection. |
| title_sort | functionality of dengue virus specific memory t cell responses in individuals who were hospitalized or who had mild or subclinical dengue infection |
| work_keys_str_mv | AT jeewandarac functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT adikarit functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT gomesl functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT fernandos functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT fernandor functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT pereram functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT ariyaratned functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT kamaladasaa functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT salimim functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT prathapans functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT oggg functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection AT malavigeg functionalityofdenguevirusspecificmemorytcellresponsesinindividualswhowerehospitalizedorwhohadmildorsubclinicaldengueinfection |