Arresting Connections

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Science  11 Feb 2005:
Vol. 307, Issue 5711, pp. 817
DOI: 10.1126/science.307.5711.817d

Our T cell repertoire is individually tailored by positive selection, during which developing thymocytes are vetted for their ability to interact appropriately with self peptides bound to major histocompatibility complex proteins. Using two-photon microscopy, Bhakta et al. scrutinized the calcium concentration and motility of thymocytes undergoing positive selection. To maintain the intricate thymic stromal environment, thymocytes were labeled with a dye and introduced into slices of intact thymic tissue. Under conditions in which positive selection did not take place, thymocytes wandered about in much the same way as naïve lymphocytes have been observed to do in lymph nodes. However, this behavior altered in positive selection environments, with thymocytes slowing down considerably and prolonging their interactions with cells of the thymic stroma. Furthermore, these thymocytes displayed increased oscillations of intracellular calcium, indicative of cellular activation. Interruption of Ca2+ signaling was sufficient to restore motility to the thymocytes, suggesting that Ca2+ is induced to promote positive selection, most likely by modifying the expression of genes that favor interactions with the thymic stroma. — SJS

Nature Immunol. 6, 143 (2005).

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