The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/10/1269/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 8, October 20, 1997 1269-1275

Articles

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

Jörg Kirberg*,{ddagger}, Anton Berns*, and Harald von Boehmer§

From the * Netherlands Cancer Institute, Division of Molecular Genetics, 1066 CX Amsterdam, The Netherlands; {ddagger} 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.

Address correspondence to Jörg Kirberg, Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, NL-1066 CX Amsterdam, The Netherlands. Phone: 0031-20-512 19 98; FAX: 0031-20-512 20 11; E-mail: kirberg{at}nki.nl

1 Abbreviations used in this paper: dGuo, 2'-deoxyguanosine; Rag, recombination activating gene; sIg, surface Ig; HSA, heat stable antigen.


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