The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/2000/1/355/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 2, January 17, 2000 355-364

Original Article

Tetracycline-controllable Selection of CD4+ T Cells: Half-Life and Survival Signals in the Absence of Major Histocompatibility Complex Class II Molecules

Deborah Witherdena, Nicolai van Oersb,c, Caroline Waltzingera, Arthur Weissb, Christophe Benoista, and Diane Mathisa
a Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), 67404 Illkirch cedex, Strasbourg, France
b Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143
c The University of Texas Southwestern Medical Center, Center for Immunology, Southwestern Medical School, Dallas, Texas 75235

Correspondence to: Christophe Benoist, I.G.B.M.C., BP 163, 67404 Illkirch cedex, France. Tel:33-3-88-65-32-00 Fax:33-3-88-65-32-46 E-mail:cbdm{at}igbmc.u-strasbg.fr.

A system that allows the study, in a gentle fashion, of the role of MHC molecules in naive T cell survival is described. Major histocompatibility complex class II–deficient mice were engineered to express E{alpha} chains only in thymic epithelial cells in a tetracycline (tet)-controllable manner. This resulted in tet-responsive display of cell surface E complexes, positive selection of CD4+8- thymocytes, and generation of a CD4+ T cell compartment in a class II–barren periphery. Using this system, we have addressed two unresolved issues: the half-life of naive CD4+ T cells in the absence of class II molecules (3–4 wk) and the early signaling events associated with class II molecule engagement by naive CD4+ T cells (partial CD3 {zeta} chain phosphorylation and ZAP-70 association).

Key Words: transgenic, lymph node, inducible expression, T lymphocyte


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