Listeria 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.
Bibliographical noteFunding Information:
The authors thank J. Walter and R. Speier for technical help, T. Martin and the CFI core flow cytometry facility for assistance with sorting and flow cytometry experiments, and K. Pape for assistance with immunohistology. This work was supported by grants to M.K.J. (NIH R01-AI39614, R37-AI27998, R01-AI66018), A.J.P. (NIH T32-AI07313 and a Kunze Fellowship), and B.Z.I. (NIH R01-AR056632 and Dermatology Foundation Fellowship).