Thymocyte emigration is mediated by active movement away from stroma-derived factors.
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.
Poznansky
Mark C
MC
AIDS Research Center and Massachusetts General Hospital Cancer Center, Building 149 13th Street, Room 4005A, Boston, MA 02129, USA. mpoznansky@partners.org
Olszak
Ivona T
IT
Evans
Richard H
RH
Wang
Zhengyu
Z
Foxall
Russell B
RB
Olson
Douglas P
DP
Weibrecht
Kathryn
K
Luster
Andrew D
AD
Scadden
David T
DT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D018920:Coculture Techniques; D005333:Fetus / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse