T-cell help dependence of memory CD8+ T-cell expansion upon vaccinia virus challenge relies on CD40 signaling.

Due to their capacity to differentiate into long-lived memory cells, CD8(+) T cells are able to resolve subsequent infections faster than during the primary response. Among other factors, CD4(+) T cells play a crucial role during primary and secondary CD8(+) T-cell responses. However, the timing and mechanisms by which they influence CD8(+) T cells may differ in primary and secondary responses. Here, we demonstrate that during both primary and secondary vaccinia virus infection, CD4(+) T cells are necessary to promote CD8(+) T-cell responses. While CD4(+) T cells contributed to memory CD8(+) T-cell development, they were even more important during memory recall responses during challenge, as absence of CD4(+) T cells during challenge resulted in markedly decreased proliferation and increased apoptosis. T-cell help during primary and secondary responses was mediated via CD40 signaling, with DCs being an integral part of that pathway. As opposed to primary CD8(+) T-cell responses where only a combination of agonistic CD40 signaling and provision of IL-2 could substitute for T-cell help, agonistic CD40 triggering alone was sufficient to rescue memory CD8(+) T-cell responses in absence of T-cell help in the context of vaccinia virus infection.

Bedenikovic G ，Crouse J ，Oxenius A 《-》

CD4(+) T-cell dependence of primary CD8(+) T-cell response against vaccinia virus depends upon route of infection and viral dose.

Hu Z ，Molloy MJ ，Usherwood EJ 《-》

Direct CD4 help provision following interaction of memory CD4 and CD8 T cells with distinct antigen-presenting dendritic cells.

de Goër de Herve MG ，Dembele B ，Vallée M ，Herr F ，Cariou A ，Taoufik Y ... -  《-》

Helping themselves: optimal virus-specific CD4 T cell responses require help via CD4 T cell licensing of dendritic cells.

Although CD4(+) T cell help (Th) is critical for inducing optimal B cell and CD8(+) T cell responses, it remains unclear whether induction of CD4(+) Th responses postinfection are also dependent on CD4(+) T cell help. In this study, we show that activation of adoptively transferred Th cells during primary influenza A virus (IAV) infection enhances both the magnitude and functional breadth of endogenous primary IAV-specific CD4(+) T cell responses. This enhancement was dependent on CD154-CD40-dependent dendritic cell licensing and resulted in a greater recall capacity of IAV-specific CD4(+) and CD8(+) T memory responses after heterologous IAV infection. These data suggest that engaging pre-existing CD4 responses at the time of priming may be a strategy for improving cellular immunity after vaccination.

Olson MR ，Seah SG ，Cullen J ，Greyer M ，Edenborough K ，Doherty PC ，Bedoui S ，Lew AM ，Turner SJ ... -  《-》

A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory.

Bourgeois C ，Rocha B ，Tanchot C 《-》