Thymocyte emigration is mediated by active movement away from stroma-derived factors
Mark C. Poznansky, … , Andrew D. Luster, David T. Scadden
Mark C. Poznansky, … , Andrew D. Luster, David T. Scadden
Published April 15, 2002
Citation Information: J Clin Invest. 2002;109(8):1101-1110. https://doi.org/10.1172/JCI13853.
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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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Fugetactic activity is present in two fractions of human TSCM prepared o...
Fugetactic activity is present in two fractions of human TSCM prepared on a cation column, one with undetectable SDF-1 and a second containing SDF-1. A 1:10 dilution of column fractions (Fxn 1–10) derived from an SP cation-ion-exchange column eluted with a linear gradient of NaCl concentration (0.1–1 M) was used in experiments. The fugetactic activity was determined using a standard transwell assay system. Each fraction was loaded into the upper chamber of the transwell alone, and the migration of CD4+ CD45RO T cells away from the fraction was quantitated as described above. Fractions 4 and 9 contained fugetactic activity for CD4+ CD45RO T cells. The fugetactic activity of fraction 9 alone was inhibitable if T cells were preincubated with anti-CXCR4. The control fugetactic activity of 1 μg/ml SDF-1 (SDF/m) and medium alone (m/m) was also tested. Each data point represents the mean and SEM of three independent experiments. Fractions of TSCM prepared on a cation-exchange column were analyzed by Western blot with a polyclonal goat anti-human SDF-1 Ab (R&D Systems Inc., Minneapolis, Minnesota, USA) and a peroxidase-conjugated secondary Ab. Only fraction 9 and control recombinant human (rHu) SDF-1 (100 ng) generated a positive band of approximately 8 kDa (inset). *P < 0.1, **P < 0.001, Student t test.