Thymocyte emigration is mediated by active movement away from stroma-derived factors
Mark C. Poznansky, Ivona T. Olszak, Richard H. Evans, Zhengyu Wang, Russell B. Foxall, Douglas P. Olson, Kathryn Weibrecht, Andrew D. Luster, David T. Scadden
Mark C. Poznansky, Ivona T. Olszak, Richard H. Evans, Zhengyu Wang, Russell B. Foxall, Douglas P. Olson, Kathryn Weibrecht, Andrew D. Luster, David T. Scadden
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Article Immunology

Thymocyte emigration is mediated by active movement away from stroma-derived factors

Abstract

T cells leave the thymus at a specific time during differentiation and do not return despite elaboration of known T cell chemoattractants by thymic stroma. We observed differentiation stage–restricted egress of thymocytes from an artificial thymus in which vascular structures or hemodynamics could not have been playing a role. Hypothesizing that active movement of cells away from a thymic product may be responsible, we demonstrated selective reduction in emigration from primary thymus by inhibitors of active movement down a concentration gradient (chemofugetaxis). Immature intrathymic precursors were insensitive to an emigration signal, whereas mature thymocytes and peripheral blood T cells were sensitive. Thymic stroma was noted to elaborate at least two proteins capable of inducing emigration, one of which was stromal cell–derived factor-1. Thymic emigration is mediated, at least in part, by specific fugetaxis-inducing factors to which only mature cells respond.

Authors

Mark C. Poznansky, Ivona T. Olszak, Richard H. Evans, Zhengyu Wang, Russell B. Foxall, Douglas P. Olson, Kathryn Weibrecht, Andrew D. Luster, David T. Scadden

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Checkerboard analysis of migratory responses of fetal T cells to TSCM. N...
Checkerboard analysis of migratory responses of fetal T cells to TSCM. Numbers shown represent mean number of cells ± SEM, from three independent experiments, that migrated through a polycarbonate membrane with a 5-μm pore size into the lower chamber of a transwell. Human fetal blood T cells were counted in the lower chamber 3 hours after the introduction of 5 × 104 cells into the upper chamber, and human TSCM was added at the indicated dilutions in the upper chamber (above diagonal), creating a negative gradient, or the lower chamber (below diagonal), creating a positive gradient. Squares along the diagonal represent cell migration in the presence of TSCM in the absence of a gradient and correspond to chemokinesis or random movement. ND, not determined.