Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.

Functional studies show that programming of CD8+ T cells occurs early after initial antigen encounter within as little as 2 hours. To define the molecular basis of these events, we transferred TCR transgenic T cells from F5 Rag-/- mice into naive recipients and stimulated them with recombinant vacci...

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Autores principales: Chiu, C, Heaps, A, Cerundolo, V, Mcmichael, A, Bangham, C, Callan, M
Formato: Journal article
Lenguaje:English
Publicado: 2007
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author Chiu, C
Heaps, A
Cerundolo, V
Mcmichael, A
Bangham, C
Callan, M
author_facet Chiu, C
Heaps, A
Cerundolo, V
Mcmichael, A
Bangham, C
Callan, M
author_sort Chiu, C
collection OXFORD
description Functional studies show that programming of CD8+ T cells occurs early after initial antigen encounter within as little as 2 hours. To define the molecular basis of these events, we transferred TCR transgenic T cells from F5 Rag-/- mice into naive recipients and stimulated them with recombinant vaccinia expressing the immunodominant influenza epitope NP366-374. Transcription in epitope-specific cytotoxic T lymphocytes (CTLs) was analyzed using Affymetrix 430 2.0 GeneChips and quantitative polymerase chain reaction (PCR). We demonstrated an early transcriptional burst with the greatest number of genes reaching peak expression 12 hours after stimulation. Using in vivo cytotoxicity assays we demonstrated that early up-regulation of cytolytic genes was accompanied by acquisition of killing capacity within 24 hours of stimulation. However, T-cell proliferation was not observed until 48 hours. We therefore conclude that clonal expansion rather than acquisition of effector function is the rate-limiting step in the development of a primary CTL response.
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spelling oxford-uuid:ac4351ef-c237-4aa0-a60c-3a31ec18280d2022-03-27T03:27:41ZEarly acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ac4351ef-c237-4aa0-a60c-3a31ec18280dEnglishSymplectic Elements at Oxford2007Chiu, CHeaps, ACerundolo, VMcmichael, ABangham, CCallan, MFunctional studies show that programming of CD8+ T cells occurs early after initial antigen encounter within as little as 2 hours. To define the molecular basis of these events, we transferred TCR transgenic T cells from F5 Rag-/- mice into naive recipients and stimulated them with recombinant vaccinia expressing the immunodominant influenza epitope NP366-374. Transcription in epitope-specific cytotoxic T lymphocytes (CTLs) was analyzed using Affymetrix 430 2.0 GeneChips and quantitative polymerase chain reaction (PCR). We demonstrated an early transcriptional burst with the greatest number of genes reaching peak expression 12 hours after stimulation. Using in vivo cytotoxicity assays we demonstrated that early up-regulation of cytolytic genes was accompanied by acquisition of killing capacity within 24 hours of stimulation. However, T-cell proliferation was not observed until 48 hours. We therefore conclude that clonal expansion rather than acquisition of effector function is the rate-limiting step in the development of a primary CTL response.
spellingShingle Chiu, C
Heaps, A
Cerundolo, V
Mcmichael, A
Bangham, C
Callan, M
Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.
title Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.
title_full Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.
title_fullStr Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.
title_full_unstemmed Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.
title_short Early acquisition of cytolytic function and transcriptional changes in a primary CD8+ T-cell response in vivo.
title_sort early acquisition of cytolytic function and transcriptional changes in a primary cd8 t cell response in vivo
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