Blimp-1 Transcription Factor Is Required for the Differentiation of Effector CD8+ T Cells and Memory Responses

Abstract

In response to viral infection, naive CD8(+) T cells proliferate and differentiate into cytotoxic and cytokine-producing effector cells. Here we showed that the transcription factor Blimp-1, a crucial regulator of plasma cell differentiation, was required for CD8(+) T cells to differentiate into functional killer T cells in response to influenza virus. Blimp-1 was not essential for the generation of memory T cells but was crucial for their efficient recall response upon reinfection. Antigen-specific Blimp-1-deficient CD8(+) T cells failed to appropriately regulate the transcriptional program essential for killer T cell responses and showed impaired migration to the site of infection. This study identifies Blimp-1 as a master regulator of the terminal differentiation of CD8(+) effector T cells and uncovers a conservation of the pathways that regulate the terminal differentiation of T and B cells.

Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

“…1A), matching our previous observations with anti-TT ASCs (11). These Blimp-1 GFP/+ cells expressed high levels of CD138, the PC marker, for the largest part were not Blimp-1 GFP/+ CD8 + T cells (25,26) and displayed the characteristic morphology of PCs (Supplemental Fig. 1B).…”

The Notch Signaling Pathway Controls Short-Lived Effector CD8+ T Cell Differentiation but Is Dispensable for Memory Generation

“…Indeed, in absence of Notch signaling, Ag-specific CD8 + effectors show a severe reduction in Further studies are required to determine whether Cd25 is a direct Notch target gene in CD8 + T cells, a likely possibility because it has been reported that the NICD can be recruited to the Cd25 promoter in double-negative thymocytes (44) and to the Cd25 enhancer in leukemic T cells (10). The maintenance of CD25 expression on a subset of effector CD8 + T cells is required for the generation of SLECs, and it was proposed, by us and others, that this was necessary to allow for the proper upregulation of Blimp-1 (3, 4), a key transcriptional repressor controlling SLEC differentiation (5,6). Unexpectedly, in our models, the defective expression of CD25 by Notch D/D effectors did not prevent the upregulation of Prdm1 transcription.…”

“…Furthermore, SLECs differentiate from effectors that have maintained the expression of the IL-2Ra chain (CD25) (3), which allows for the induction of the expression of the transcriptional repressor Blimp-1 (3,4), a key molecule controlling SLEC differentiation (5,6). Although the cytokine milieu plays a very important role during the differentiation of effectors, it is still possible that other receptor-ligand interaction provided by APCs may also play a crucial role during the differentiation of naive CD8 + T cells into Te and Tm cells.…”

Oct1 and OCA-B are selectively required for CD4 memory T cell function

“…CD4 + memory T cells persist for long periods and provide protection as both central/circulating and tissue-resident cells (Hammarlund et al, 2003;Darrah et al, 2007;Williams et al, 2008;Pepper et al, 2011;Iijima and Iwasaki, 2014;Zens and Farber, 2015). Although transcription regulators such as T-bet, Eomes, Blimp-1, Bcl-6, STAT3, and Foxo1 have been implicated in the generation of T cell memory, mostly in CD8 + cells (Ichii et al, 2002(Ichii et al, , 2007Intlekofer et al, 2007;Joshi et al, 2007;Kallies et al, 2009;Rutishauser et al, 2009;Banerjee et al, 2010;Cui et al, 2011;Rao et al, 2012;Hess Michelini et al, 2013), little is known regarding the mechanism, in particular with respect to CD4 memory. Furthermore, factors selectively regulating memory cell populations are not well described.…”