CD154+ CD4+ T-cell dependence for effective memory influenza virus-specific CD8+ T-cell responses

Matthew R Olson, Shirley G K Seah, Kathryn M. Edenborough, Peter C Doherty, Andrew M Lew, Stephen J. Turner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

CD40-CD154 (CD40 ligand) interactions are essential for the efficient priming of CD8 + cytotoxic T lymphocyte (CTL) responses. This is typically via CD4 + CD154 + T-cell-dependent 'licensing' of CD40 + dendritic cells (DCs); however, DCs infected with influenza A virus (IAV) upregulate CD154 expression, thus enabling efficient CTL priming in the absence of CD4 + T activation. Therefore, it is unclear whether CD4 T cells and DCs have redundant or unique roles in the priming of primary and secondary CTL responses after infection. Here we determine the precise cellular interactions involved in CD40-CD154 regulation of both primary and secondary IAV-specific CTL responses. Infection of both CD40 KO and CD154 KO mice resulted in diminished quantitative and qualitative CTL responses after both primary and secondary infection. Adoptive transfer of CD154 +, but not CD154 KO, CD4 T cells into CD154 KO mice restored both primary and secondary IAV-specific CD8 T-cell responses. These data show that, although CD154 expression on CD4 T cells and other cell types (that is, DCs) may be redundant for the priming of primary CTL responses, CD154 expression by CD4 T cells is required for the priming memory CD8 T cells that are capable of fully responding to secondary infection.

Original languageEnglish
Pages (from-to)605-611
Number of pages7
JournalImmunology and Cell Biology
Volume92
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

Cite this

Olson, Matthew R ; Seah, Shirley G K ; Edenborough, Kathryn M. ; Doherty, Peter C ; Lew, Andrew M ; Turner, Stephen J. / CD154+ CD4+ T-cell dependence for effective memory influenza virus-specific CD8+ T-cell responses. In: Immunology and Cell Biology. 2014 ; Vol. 92, No. 7. pp. 605-611.
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abstract = "CD40-CD154 (CD40 ligand) interactions are essential for the efficient priming of CD8 + cytotoxic T lymphocyte (CTL) responses. This is typically via CD4 + CD154 + T-cell-dependent 'licensing' of CD40 + dendritic cells (DCs); however, DCs infected with influenza A virus (IAV) upregulate CD154 expression, thus enabling efficient CTL priming in the absence of CD4 + T activation. Therefore, it is unclear whether CD4 T cells and DCs have redundant or unique roles in the priming of primary and secondary CTL responses after infection. Here we determine the precise cellular interactions involved in CD40-CD154 regulation of both primary and secondary IAV-specific CTL responses. Infection of both CD40 KO and CD154 KO mice resulted in diminished quantitative and qualitative CTL responses after both primary and secondary infection. Adoptive transfer of CD154 +, but not CD154 KO, CD4 T cells into CD154 KO mice restored both primary and secondary IAV-specific CD8 T-cell responses. These data show that, although CD154 expression on CD4 T cells and other cell types (that is, DCs) may be redundant for the priming of primary CTL responses, CD154 expression by CD4 T cells is required for the priming memory CD8 T cells that are capable of fully responding to secondary infection.",
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CD154+ CD4+ T-cell dependence for effective memory influenza virus-specific CD8+ T-cell responses. / Olson, Matthew R; Seah, Shirley G K; Edenborough, Kathryn M.; Doherty, Peter C; Lew, Andrew M; Turner, Stephen J.

In: Immunology and Cell Biology, Vol. 92, No. 7, 2014, p. 605-611.

Research output: Contribution to journalArticleResearchpeer-review

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