The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/1/117/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 1, January 5, 1998 117-122

Brief Definitive Reports

Activity and Phenotype of Natural Killer Cells in Peptide Transporter (TAP)-deficient Patients (Type I Bare Lymphocyte Syndrome)

Jacques Zimmer*, Lionel Donato{ddagger}, Daniel Hanau*, Jean-Pierre Cazenave*, Marie-Marthe Tongio*, Alessandro Moretta§, and Henri de la Salle*

From the * Laboratoire d'Histocompatibilité, Contrat Jeune Formation Institut National de la Santé et de la Recherche Médicale 94-03, and Institut National de la Santé et de la Recherche Médicale U.311, Etablissement de Transfusion Sanguine, Strasbourg 67065, France; {ddagger} Service de Pédiatrie, Hôpital de Hautepierre, Strasbourg 67098, France; and § Istituto di Istologia ed Embriologia Generale, Università di Genova, 16132 Genova, Italy and Dipartimento di Scienze Biomediche e Biotechnologie, Università di Brescia, 25100 Brescia, Italy

In this paper we describe the function and phenotype of natural killer (NK) lymphocytes from HLA class I–deficient patients. These cells are, as has been previously reported, unable to lyse HLA class I– K562 cells, but are able to perform antibody-dependent cellular cytotoxicity (ADCC), although with lower efficiency as compared to NK cells from normal individuals. Transporter associated to antigen processing (TAP)– NK cells proliferate when cultured in the presence of lymphoblastoid B cells (B-LCs) and interleukin 2 and develop a spectrum of cytotoxicity similar to that of activated normal NK cells. Importantly, activation of the TAP– NK cells induces strong cytotoxicity to autologous B-LCs. Analysis of the phenotype of circulating TAP– NK lymphocytes showed them to display a normal diverse repertoire of HLA class I–specific NK receptors. These receptors were expressed at normal levels, apart from the CD94–NKG2A complex, which appeared to be overexpressed. This latter finding could reflect an adaptation to the low expression of HLA class I molecules. Finally, functional analyses indicated that the inhibitory receptors in TAP– individuals can transduce inhibitory signals. Our results suggest that in vivo, the NK cells of TAP– patients could participate in immune defense, at least through ADCC, but upon activation, may be involved in autoimmune processes.

Address correspondence to Henri de la Salle, ETS de Strasbourg, 10 rue Spielmann BP No. 36, 67065 Strasbourg Cedex, France. Phone: 33-3-88-21-25-25; FAX: 33-3-88-21-25-44; E-mail: henri.delasalle{at}etss.u-strasbg.fr

J. Zimmer was the recipient of a grant (BFR 96/003) from the Ministère de l'Education Nationale et de la Formation Professionnelle, Luxembourg. This work was supported by the Etablissement de Transfusion Sanguine de Strasbourg (Strasbourg, France), and by Institut National de la Santé et de la Recherche Médicale (CJF 94-03).


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