Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation.

Journal article

CD8+ T cells play a crucial role in controlling intracellular pathogens. The level of memory CD8+ T cells developing after vaccination or infection influences the degree of T cell-mediated protection after secondary infection. We used defined animal models and infections/immunizations by replicating or non-replicating antigens to define on a molecular and cellular level in vivo the parameters that identify and shape long-lived CD8+ T cell memory. We show that the timing of antigen exposure during vaccination is key for the induction of long-lived T cell memory. Brief antigen exposure induced high numbers of effector cells but limited development of long-lived CD8+ memory T cells. In contrast, prolonged antigen exposure for up to 9 days induced similar numbers of effector T cells but additionally resulted in high levels of memory CD8+ T cells. Unexpectedly CD127 (IL-7Ralpha) expression on CD8+ T cells during the acute priming phase was a necessary but not sufficient requirement for entering the pool of long-lived antigen-independent memory CD8+ T cells. However, we provide strong evidence for the interpretation that programming of long-lived memory T cells was driven by low levels of transcription factor eomesodermin and protease inhibitor Spi2A as well as reduced phosphorylation of c-JUN.

Authors: Bachmann, M; Beerli, R; Agnellini, P; Wolint, P; Schwarz, K

• Publication status: Published
• Journal: European journal of immunology
• Volume: 36
• Issue: 4
• Pages: 842-854
• Publication date: 2006-04-01
• DOI: 10.1002/eji.200535730
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Serpins; Receptors, Interleukin-7; Fluorescent Antibody Technique; Reverse Transcriptase Polymerase Chain Reaction; Animals; Mice; Mice, Inbred C57BL; Lymphocytic choriomeningitis virus; Xenopus Proteins; Antigens; Gene Expression; Lymphocyte Activation; Vaccines; Antigens, Viral; CD8-Positive T-Lymphocytes; Immunologic Memory; Phosphorylation; T-Box Domain Proteins; JNK Mitogen-Activated Protein Kinases