Immunology Separating Immune Cell Fate

Helen Pickersgill

Science, AAAS, Cambridge CB2 1LQ, UK

The adaptive immune response is mediated in part by CD8⁺ T cells, which protect against intracellular infection by pathogens and against some tumors. This T cell population fulfills a dual function by providing immediate protection via effector cells and retaining this protective immunity long-term via memory cells. On infection, naïve T cells carrying pathogen-specific T cell receptors (TCR) differentiate into short-lived effector cells and long-lived memory cells. However, it is unclear how this is regulated and whether memory cells are formed from the effector cells or differentiate separately (see the Perspective by Feau and Schoenberger). Teixeiro et al. have now shown a direct role for the TCR specifically in CD8⁺ memory T cell differentiation. Upon bacterial infection of mice harboring defective TCRs, mutant T cells were still able to generate effector T cells and a robust primary immune response but were specifically impaired in developing memory T cells. Thus, the differentiation of effector and memory CD8⁺ T cells is separable and determined by the induction of a distinct set of TCR signals. However, Bannard et al. used a transgenic mouse line to closely map the cell fate of a subset of effector T cells that were generated during the primary response to infection by influenza. These effector cells were found to survive and become memory cells that could replicate and expand during secondary infection.

E. Teixeiro, M. A. Daniels, S. E. Hamilton, A. G. Schrum, R. Bragado, S. C. Jameson, E. Palmer, Different T cell receptor signals determine CD8⁺ memory versus effector development. Science 323, 502–505 (2009). [Abstract] [Full Text]

O. Bannard, M. Kraman, D. T. Fearon, Secondary replicative function of CD8⁺ T cells that had developed an effector phenotype. Science 323, 505–509 (2009). [Abstract] [Full Text]

S. Feau, S. P. Schoenberger, Ex uno plura. Science 323, 466–467 (2009). [Summary] [Full Text]