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CD44^high Memory CD8 T Cells Synergize with CpG DNA to Activate Dendritic Cell IL-12p70 Production¹

Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore

Protective memory CD8 T cell responses are generally associated with the rapid and efficient acquisition of CTL function. However, the ability of memory CD8 T cells to modulate immune responses through interactions with dendritic cells (DCs) during the early states of secondary Ag exposure is poorly understood. In this study, we show that murine Ag-specific CD44^high CD8 T cells, representing CD8 T cells of the memory phenotype, potently activate DCs to produce high levels of IL-12p70 in conjunction with stimulation of DCs with the TLR 9 ligand, unmethylated CpG DNA. IL-12p70 production was produced predominantly by CD8⁺ DCs and plasmacytoid DCs, and mediated by CD8 T cell-derived cytokines IFN-, GM-CSF, TNF-, and surface CD40L. We also find that CD44^high memory phenotype CD8 T cells were better DC IL-12p70 stimulators than CD44^low naive phenotype CD8 T cells, and this was attributed to higher levels of IFN- and GM-CSF produced by CD44^high memory phenotype CD8 T cells during their Ag specific interaction with DCs. Our study identifies CpG DNA as the most effective TLR ligand that cooperates with CD8 T cells for DC IL-12p70 production, and suggests that effectiveness of memory CD8 T cells could be attributed to their ability to rapidly and effectively induce protective Th1 immunity during early stages of pathogen reinfection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work is funded by the Biomedical Research Council (Grant No. 04/1/21/19/373) and the Life Sciences Institute, National University of Singapore (to D.M.K.). K.L.W. was supported by an A*STAR graduate scholarship.

² K.L.W. and L.F.M.T. contributed equally to this study.

³ Address correspondence and reprint requests to Prof. David M. Kemeny, Immunology Programme and Department of Microbiology, Centre for Life Sciences, #03-05, 28 Medical Drive, National University of Singapore, Singapore. E-mail address: mickdm{at}nus.edu.sg

⁴ Abbreviations used in this paper: DC, dendritic cell; cDC, classical DC; pDC, plasmacytoid DC; 7-AAD, 7-amino-actinomycin D; poly I:C, polyinosinic: polycytidylic acid.