In Vivo Expression of Natural Killer Cell Inhibitory Receptors by Human Melanoma–specific Cytolytic T Lymphocytes

doi:10.1084/jem.190.6.775

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© The Rockefeller University Press, 0022-1007/1999/9/775/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 775-782

In Vivo Expression of Natural Killer Cell Inhibitory Receptors by Human Melanoma–specific Cytolytic T Lymphocytes

Daniel E. Speiser^a, Mikaël J. Pittet^a, Danila Valmori^a, Rod Dunbar^b, Donata Rimoldi^c, Danielle Liénard^a,d, H. Robson MacDonald^c, Jean-Charles Cerottini^a,c, Vincenzo Cerundolo^b, and Pedro Romero^a
^a Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
^b Institute of Molecular Medicine, Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom
^c Ludwig Institute for Cancer Research, Lausanne Branch, 1066 Epalinges, Switzerland
^d Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland

Correspondence to: Daniel E. Speiser, Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, CHUV - BH 19-602, CH-1011 Lausanne, Switzerland. Tel:41-21-314-01-82 Fax:41-21-314-74-77 E-mail:daniel.speiser{at}hospvd.ch.

Natural killer (NK) receptor signaling can lead to reduced cytotoxicityby NK cells and cytolytic T lymphocytes (CTLs) in vitro. WhetherT cells are inhibited in vivo remains unknown, since peptideantigen–specific CD8⁺ T cells have so far not been foundto express NK receptors in vivo. Here we demonstrate that melanomapatients may bear tumor-specific CTLs expressing NK receptors.The lysis of melanoma cells by patient-derived CTLs was inhibitedby the NK receptor CD94/NKG2A. Thus, tumor-specific CTL activitymay be decreased through NK receptor triggering in vivo.

Key Words: cytolytic T lymphocytes, natural killer receptors, melanoma,tumor immunity, peptide antigen

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