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© The Rockefeller University Press, 0022-1007/1999/10/1039/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 8, October 18, 1999 1039-1048

Original Article

Pre–T Cell Receptor (Tcr) and Tcr-Controlled Checkpoints in T Cell Differentiation Are Set by Ikaros

Susan Winandya, Li Wub, Jin-Hong Wanga, and Katia Georgopoulosa

a Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129
b The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Bldg. 149, 13th St., Charlestown, MA 02129.617-726-4453617-726-4445

katia.georgopoulos{at}cbrc2.mgh.harvard.edu

T cell differentiation relies on pre–T cell receptor (TCR) and TCR signaling events that take place at successive steps of the pathway. Here, we show that two of these T cell differentiation checkpoints are regulated by Ikaros. In the absence of Ikaros, double negative thymocytes can differentiate to the double positive stage without expression of a pre-TCR complex. Subsequent events in T cell development mediated by TCR involving transition from the double positive to the single positive stage are also regulated by Ikaros. Nonetheless, in Ikaros-deficient thymocytes, the requirement of pre-TCR expression for expansion of immature thymocytes as they progress to the double positive stage is still maintained, and the T cell malignancies that invariably arise in the thymus of Ikaros-deficient mice are dependent on either pre-TCR or TCR signaling. We conclude that Ikaros regulates T cell differentiation, selection, and homeostasis by providing signaling thresholds for pre-TCR and TCR.

Key Words: thymocyte • selection • signaling • homeostasis • malignancy

1used in this paper: DN, Ikaros dominant negative mutation; HPRT, hypoxanthine-guanine phosphoribosyltransferase; RAG, recombinase activating gene; RT, reverse transcriptase

J.-H. Wang's current address is Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ 08453-4000.

© 1999 The Rockefeller University Press


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