Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells

Abstract

Naïve T cells proliferate and differentiate into memory cells after antigenic stimulation or in a lymphopenic environment. We showed here transient increases in memory phenotype CD8+ T cell numbers in the lymphopenic environment of spleens of very young mice. The magnitude of the increase correlated with Bcl-6 expression in the T cells. Bcl-6 controlled the generation and maintenance of antigen-specific memory phenotype CD8+ T cells in the spleens of immunized mice. These data suggest that Bcl-6, which is essential for memory B cell development in germinal centers, is a key molecule for the establishment not only of memory T cells but also of the peripheral T cell compartment in infancy.

Bcl6 controls granzyme B expression in effector CD8+ T cells

“…Thus, control of the protease activity in effector CD8 + T cells and rescue of effector CD8 + T cells from the programmed cell death are critical to generate memory CD8 + T cells. Since we have demonstrated that Bcl6 plays a role in generation of memory CD8 + T cells [21,22], reduction of granzyme B production in effector CD8 + T cells by Bcl6 may explain the role for Bcl6. Further study is required to determine the relation between the regulation of granzyme B production in effector CD8 + T cells by Bcl6 and the generation of memory CD8 + T cells.…”

“…Bcl6 -/- [17] and lck-Bcl6 Tg [21] mice were backcrossed to C57BL/6 mice more than ten generations. C57BL/6 (B6-Ly5.1) mice were purchased from Charles River Japan.…”

“…We have recently reported that the IL-5 gene in T cells [19] and the IL-18 gene in macrophages [20] are the molecular targets of Bcl6. Furthermore, Tg mice carrying the murine Bcl6 cDNA under the control of the murine lck-proximal promoter (lck-Bcl6) demonstrated that Bcl6 plays a role in the generation and maintenance of memory CD8 + T cells during both antigen-and lymphopenia-induced activation [21]. Functional properties of memory CD8 + T cells generated in lck-Bcl6 Tg mice are central memory CD8 + T cells [22].…”

Defect of CD8+ Memory T Cells Developed in Absence of IL-12 Priming for Secondary Expansion

“…Bcl-6 is essential for memory B cell development in germinal center (16). It has recently been demonstrated that Bcl-6 also plays a role in generation and maintenance of CD8 + Tm cells induced in responses to Ag stimulation (17). More recently, it has been shown that CD8 + Tm cells developed in the absence of CD4 + Th cells have a defective response for rapid cytokine production upon re-encounter with Ag and exhibit increased DNA methylation at the IL-2 promoter region (18), indicating that epigenetic modeling provides a molecular basis for the maintenance of a "ready-to-respond" state of CD8 + Tm cells.…”

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

“…1 These effector T-cell subsets are driven by distinct networks: a transcriptional program involving Blimp1, Id2 and t-bet is critical for the generation of KLRG1 hi CD127 lo effector cells, [1][2][3][4] whereas an alternative transcriptional program involving Bcl-6, STAT3, eomoesodermin, Id3 and T-cell factor-1 are critical for the generation of KLRG1 lo CD127 hi pre-memory cells. [5][6][7][8][9][10] Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, the results are complicated by the fact that little work has been done examining effector CD8 þ T-cell responses in mice whose death programs have been disabled.…”