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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(a) Emigration of thymocyte and peripheral blood T cells from the thymic...
(a) Emigration of thymocyte and peripheral blood T cells from the thymic organoid. Purified human (Hu) CD4+ and CD8+ SP thymocytes, DP CD4+CD8+ thymocytes, and fetal blood T cells were plated onto a grid coated with thymic stroma in the upper chamber of a transwell. Emigration from the upper chamber into the lower chamber was quantitated (black bars). Cells in the upper chamber were also pretreated with PTX (light gray bars), or TSCM was added to the upper and lower chambers before the addition of thymocytes (dark gray bars). Thymocyte populations or fetal blood T cells were also plated into the upper chamber in the absence of thymic stroma (white bars). The percentage of cells emigrating under each condition was assessed in three independent experiments, and the mean migration with SE bars is shown. (b) Emigration of thymocytes and peripheral blood T cells from murine (Mu) thymic fragments. Murine thymic fragments were placed in the upper chamber of a transwell. Emigration of TN (CD3–CD4–CD8–), DP (CD4+CD8+), and SP (CD4+ and CD8+) thymocytes from the thymic fragment into the lower chamber was quantitated (black bars). Thymic fragments in the upper chamber were also pretreated with PTX (light gray bars), murine TSCM was added to the upper and lower chambers prior to the addition of the fragment (dark gray bars), or thymic fragments were pretreated with paraformaldehyde (PF) (white bars). The percentage of cells emigrating under each condition was assessed in three independent experiments. The mean migration with SE bars is shown.