Non-Hematopoietic Cells in Lymph Nodes Drive Memory CD8 T Cell Inflation during Murine Cytomegalovirus Infection

PLoS Pathogens

Thomas Rülicke¹  Senta M. Walton²  Annette Oxenius²  Nicole Torti²  Thomas Brocker³ 

[1] Institute of Laboratory Animal Science and Biomodels Austria, University of Veterinary Medicine Vienna, Vienna, Austria;Institute of Microbiology, ETH Zürich, Zürich, Switzerland;Ludwig-Maximilians-University, Munich, Germany

关键词: T cells;    Cytotoxic T cells;    Lymph nodes;    Antigen presentation;    Memory T cells;    Spleen;    Viral persistence;    latency;    Viral replication;   

DOI  :  10.1371/journal.ppat.1002313

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

During human and murine cytomegalovirus (MCMV) infection an exceptionally large virus-specific CD8 T cell pool is maintained in the periphery lifelong. This anomalous response is only seen for specific subsets of MCMV-specific CD8 T cells which are referred to as 'inflationary T cells'. How memory CD8 T cell inflation is induced and maintained is unclear, though their activated phenotype strongly suggests an involvement of persistent antigen encounter during MCMV latency. To dissect the cellular and molecular requirements for memory CD8 T cell inflation, we have generated a transgenic mouse expressing an MHC class I-restricted T cell receptor specific for an immunodominant inflationary epitope of MCMV. Through a series of adoptive transfer experiments we found that memory inflation was completely dependent on antigen presentation by non-hematopoietic cells, which are also the predominant site of MCMV latency. In particular, non-hematopoietic cells selectively induced robust proliferation of inflationary CD8 T cells in lymph nodes, where a majority of the inflationary CD8 T cells exhibit a central-memory phenotype, but not in peripheral tissues, where terminally differentiated inflationary T cells accumulate. These results indicate that continuous restimulation of central memory CD8 T cells in the lymph nodes by infected non-hematopoietic cells ensures the maintenance of a functional effector CD8 T pool in the periphery, providing protection against viral reactivation events.

【 授权许可】

CC BY