APCs expressing high levels of programmed death ligand 2 sustain the development of CD4 T cell memory

Jason S. Ellis, F. Betul Guloglu, Danielle M. Tartar, Christine M. Hoeman, Cara L. Haymaker, Jason A. Cascio, Xiaoxiao Wan, Mermagya Dhakal, Amie VanMorlan, Seung Hi Yahng, Habib Zaghouani

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The role APCs play in the transition of T cells from effector to memory remains largely undefined. This is likely due to the low frequency at which long-lived T cells arise, which hinders analysis of the events involved in memory development. In this study, we used TCR transgenic T cells to increase the frequency of long-lived T cells and developed a transfer model suitable for defining the contribution of APCs to the development of CD4 T cell memory. Accordingly, naive TCR transgenic T cells were stimulated in vitro with Ag presented by different types of APCs and transferred into MHC class II-deficient mice for parking, and the hosts were later analyzed for long-lived T cell frequency or challenged with suboptimal dose of Ag, and the long-lived cells-driven memory responses were measured. The findings indicate that B cells and CD8a+ dendritic cells sustained elevated frequencies of long-lived T cells that yielded rapid and robust memory responses upon rechallenge with suboptimal dose of Ag. Furthermore, both types of APCs had significant programmed death (PD) ligand 2 expression prior to Ag stimulation, which was maintained at a high level during presentation of Ag to T cells. Blockade of PD ligand 2 interaction with its receptor PD-1 nullified the development of memory responses. These previously unrecognized findings suggest that targeting specific APCs for Ag presentation during vaccination could prove effective against microbial infections.

Original languageEnglish
Pages (from-to)3149-3157
Number of pages9
JournalJournal of Immunology
Volume185
Issue number6
DOIs
StatePublished - Sep 15 2010

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    Ellis, J. S., Betul Guloglu, F., Tartar, D. M., Hoeman, C. M., Haymaker, C. L., Cascio, J. A., Wan, X., Dhakal, M., VanMorlan, A., Yahng, S. H., & Zaghouani, H. (2010). APCs expressing high levels of programmed death ligand 2 sustain the development of CD4 T cell memory. Journal of Immunology, 185(6), 3149-3157. https://doi.org/10.4049/jimmunol.1000810