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The Journal of Experimental Medicine 192 4 Cover picture: Regulation of naive CD8⁺ T cell homeostasis by self-major histocompatibility complex (MHC)/peptide ligands. In the thymus, immature CD4⁺CD8⁺ double positive cells that interact with low affinity for MHC class I molecules loaded with self-peptides become positively selected and differentiate into mature CD8⁺ single positive cells. Upon exit to the periphery, CD8⁺ cells continuously receive low-level signals through the T cell receptor (TCR). Under physiological conditions with normal numbers of T cells, such TCR signals are insufficient to induce entry into cell cycle but adequate to keep cells alive (bottom). If the number of T cells drops below a certain level, however, TCR signals become overtly stimulatory and induce T cells to undergo a slow form of �homeostatic� proliferation (middle). Upon restoration of the naive T cell pool, homeostatic proliferation stops and some CD8⁺ clones revert to a naive phenotype, whereas others do not. Generation of �conventional� memory cells through T cell interaction with foreign peptide is qualitatively different (top). Artwork by Bob Crimi. See related article in this issue by Surh and Sprent, pp. F9-F14.
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