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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1269/07 $2.00
Volume 186, Number 8, October 20, 1997 1269-1275

Peripheral T Cell Survival Requires Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex-Encoded Molecules

By Jörg Kirberg,*Dagger Anton Berns,* and Harald von Boehmer§

From the * Netherlands Cancer Institute, Division of Molecular Genetics, 1066 CX Amsterdam, The Netherlands; Dagger  Basel Institute for Immunology, 4005 Basel, Switzerland; and § Institute Necker, INSERM 373, F-75730 Paris Cedex 15, France

In the thymus, T cells are selected according to their T cell receptor (TCR) specificity. After positive selection, mature cells are exported from primary lymphoid organs to seed the secondary lymphoid tissue. An important question is whether survival of mature T cells is an intrinsic property or requires continuous survival signals, i.e., engagement of the TCR by major histocompatibility complex (MHC) molecules in the periphery, perhaps in a similar way as occurring during thymic positive selection. To address this issue we used recombination-activating gene (Rag)-deficient H-2b mice expressing a transgenic TCR restricted by I-Ed class II MHC molecules. After engraftment with Rag-/- H-2d fetal thymi, CD4+8- peripheral T cells emerged. These cells were isolated and transferred into immunodeficient hosts of H-2b or H-2d haplotype, some of the latter being common cytokine receptor gamma  chain deficient to exclude rejection of H-2b donor cells by host natural killer cells. Our results show that in the absence, but not in the presence, of selecting MHC molecules, peripheral mature T cells are short lived and disappear within 7 wk, indicating that continuous contact of the TCR with selecting MHC molecules is required for survival of T cells.


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