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 ... -  《-》

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

Olson MR ，Seah SG ，Edenborough K ，Doherty PC ，Lew AM ，Turner SJ ... -  《-》

Influenza-induced, helper-independent CD8+ T cell responses use CD40 costimulation at the late phase of the primary response.

Seah SG ，Brady JL ，Carrington EM ，Ng WC ，Sutherland RM ，Hancock MS ，La Gruta NL ，Brown LE ，Turner SJ ，Lew AM ，Zhan Y ... -  《-》

CD4+ T helper cells use CD154-CD40 interactions to counteract T reg cell-mediated suppression of CD8+ T cell responses to influenza.

Ballesteros-Tato A ，León B ，Lund FE ，Randall TD ... -  《-》

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 《-》