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Shared reactivity of V2^neg T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells

¹ UMR 5164, Centre National de la Recherche Scientifique (CNRS), IFR 66, Université Bordeaux 2, 33076 Bordeaux, France
² Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53114 Wroclaw, Poland
³ Institut National de la Santé et de la Recherche Medicale (INSERM) U131, 92140 Clamart, France
⁴ INSERM U725, EFS Alsace, 67065 Strasbourg, France
⁵ Department of Renal Transplantation, CHU Bordeaux, 33076 Bordeaux, France
⁶ Department of Thoracic Surgery, CHU Bordeaux, 33076 Bordeaux, France

CORRESPONDENCE Julie Déchanet-Merville: julie.dechanet{at}u-bordeaux2.fr

Long-lasting expansion of V2^neg T cells is a hallmark of cytomegalovirus (CMV) infection in kidney transplant recipients. The ligands of these cells and their role remain elusive. To better understand their immune function, we generated T cell clones from several transplanted patients. Numerous patient V1⁺, V3⁺, and V5⁺ T cell clones expressing diverse V chains, but not control V9V2⁺ T clones, displayed strong reactivity against CMV-infected cells, as shown by their production of tumor necrosis factor-. V2^neg T lymphocytes could also kill CMV-infected targets and limit CMV propagation in vitro. Their anti-CMV reactivity was specific for this virus among herpesviridae and required T cell receptor engagement, but did not involve major histocompatibility complex class I molecules or NKG2D. V2^neg T lymphocytes expressed receptors essential for intestinal homing and were strongly activated by intestinal tumor, but not normal, epithelial cell lines. High frequencies of CMV- and tumor-specific V2^neg T lymphocytes were found among patients' T cells. In conclusion, V2^neg T cells may play a role in protecting against CMV and tumors, probably through mucosal surveillance of cellular stress, and represent a population that is largely functionally distinct from V9V2⁺ T cells.

F. Halary and V. Pitard contributed equally to this work.

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