The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/10/1277/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 8, October 20, 1997 1277-1285

Articles

The Common Cytokine Receptor {gamma} Chain Controls Survival of {gamma}/{delta} T Cells

Marie Malissen*, Pablo Pereira{ddagger}, David J. Gerber§, Bernard Malissen*, and James P. DiSanto||

From the * Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale–Centre National de la Recherche Scientifique de Marseille Luminy, Case 906, 13288 Marseille Cedex 9, France; {ddagger} Unité d'Immunologie, Centre National de la Recherche Scientifique Unité Recherche Associée 1961, Institut Pasteur, 75724 Paris, France; § Center for Cancer Research, Massachusetts Institute of Technology, 02139 Cambridge, Massachusetts; and || INSERM U429, Hôpital Necker-Enfants Malades, 75743 Paris, France

We have investigated the role of common {gamma} chain ({gamma}c)-signaling pathways for the development of T cell receptor for antigen (TCR)-{gamma}/{delta} T cells. TCR-{gamma}/{delta}–bearing cells were absent from the adult thymus, spleen, and skin of {gamma}c-deficient ({gamma}c–) mice, whereas small numbers of thymocytes expressing low levels of TCR-{gamma}/{delta} were detected during fetal life. Recent reports have suggested that signaling via interleukin (IL)-7 plays a major role in facilitating TCR-{gamma}/{delta} development through induction of V-J (variable-joining) rearrangements at the TCR-{gamma} locus. In contrast, we detected clearly TCR-{gamma} rearrangements in fetal thymi from {gamma}c– mice (which fail to signal in response to IL-7) and reduced TCR-{gamma} rearrangements in adult {gamma}c thymi. No gross defects in TCR-{delta} or TCR-β rearrangements were observed in {gamma}c– mice of any age. Introduction of productively rearranged TCR V{gamma}1 or TCR V{gamma}1/V{delta}6 transgenes onto mice bearing the {gamma}c mutation did not restore TCR-{gamma}/{delta} development to normal levels suggesting that {gamma}c-dependent pathways provide additional signals to developing {gamma}/{delta} T cells other than for the recombination process. Bcl-2 levels in transgenic thymocytes from {gamma}c– mice were dramatically reduced compared to {gamma}c+ transgenic littermates. We favor the concept that {gamma}c-dependent receptors are required for the maintenance of TCR-{gamma}/{delta} cells and contribute to the completion of TCR-{gamma} rearrangements primarily by promoting survival of cells committed to the TCR-{gamma}/{delta} lineage.

Address correspondence to James P. DiSanto, INSERM U429, Pavillon Kirmisson, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, Paris F-75743 France. Phone: 33-1-44-49-50-51; FAX: 33-1-45-75-13-02; E-mail: disanto{at}necker.fr

1 Abbreviations used in this paper: {gamma}c, common {gamma} chain; DETC, dendritic epidermal T cell; DN, double negative; HSA, heat-stable antigen; J, joining; RAG, recombinase-activating gene; Tg, transgenic; TSLP, thymic stromal cell–derived lymphopoeitin; V, variable; wt, wild type.


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