Young T cells receive survival signals through their T cell receptors during development. These signals are normally provided by epithelial cells in the thymus. But recent reports show that CD4⁺ thymocytes also signal to each other.

When stimulated by antigen, epithelium-educated CD4⁺ thymocytes can become helper T cells of all varieties—T helper (Th)-1, Th2, or Th17 cells—depending largely on the surrounding cytokines. But self-educated thymocytes, Li et al. now find, fail to make this lineage choice. These cells rapidly generated both interferon (IFN)- and interleukin (IL)-4, even when stimulated under conditions that normally inhibit IL-4 production. A ready-to-fire IL-4 locus and preformed IL-4 mRNA in the developing cells explained their tendency to continue synthesizing IL-4.

Mice whose thymocytes were forced to signal to each other to survive were less likely to develop allergic inflammation than were mice whose T cells developed normally. This protective effect might be due, the authors speculate, to the suppression of pro-allergic IL-4 by the IFN produced by these cells. Thus, people who have more self-educated T cells may be less allergy prone. But assessing the relative numbers of the two cell types in humans is difficult, as distinguishing surface markers have yet to be identified.

The team is now investigating how T cells decide between a thymocyte- and an epithelial cell–based education and how thymocyte-to-thymocyte signals set the cells up for an IL-4–producing future.

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Thymic selection pathway regulates the effector function of CD4 T cells

Wei Li, M. Hanief Sofi, Norman Yeh, Sarita Sehra, Brian P. McCarthy, Dipak R. Patel, Randy R. Brutkiewicz, Mark H. Kaplan, and Cheong-Hee Chang
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