Opposing Signals from the Bcl6 Transcription Factor and the Interleukin-2 Receptor Generate T Helper 1 Central and Effector Memory Cells

SummaryListeria monocytogenes infection generates T helper 1 (Th1) effector memory cells and CC chemokine receptor 7 (CCR7)+ cells resembling central memory cells. We tracked endogenous L. monocytogenes-specific CD4+ T cells to determine how these memory cells are formed. Two effector cell populations were already present several days after infection. One highly expressed the T-bet transcription factor and produced Th1 memory cells in an interleukin-2 (IL-2) receptor-dependent fashion. The other resided in the T cell areas, expressed CCR7 and CXC chemokine receptor 5 (CXCR5), and like follicular helper cells depended on the Bcl6 transcription factor and inducible costimulator ligand on B cells. The CCR7+CXCR5+ effector cells produced similar memory cells that generated diverse effector cell populations in a secondary response. Thus, Th1 effector memory and follicular helper-like central memory cells are produced from early effector cell populations that diverge in response to signals from the IL-2 receptor, Bcl6, and B cells.

Graphical AbstractFigure optionsDownload high-quality image (155 K)Download as PowerPoint slideHighlights
► Bacterial infection induces central and effector CD4+ memory T cells
► Central memory cells resemble but are distinct from follicular helper cells
► Effector memory cell formation is IL-2 dependent and Bcl6 independent
► Central memory cell formation is Bcl6 and B cell ICOSL dependent