The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion

Michael T. Wilson1, Cecilia Johansson1, Danyvid Olivares‐Villagómez1, Avneesh K. Singh1, Aleksandar K. Stanic1, Chyung‐Ru Wang1, Sebastian Joyce1, Mary Jo Wick1, Luc Van Kaer1
1Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; Department of Clinical Immunology, Göteborg University, SE-413 46 Göteborg, Sweden; and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637

Tóm tắt

CD1d-restricted natural killer T (NKT) cells are a subset of regulatory T cells that react with glycolipid antigens. Although preclinical studies have effectively targeted NKT cells for immunotherapy, little is known regarding the earlyin vivoresponse of these cells to antigenic stimulation. We have analyzed the early response of NKT cells to glycolipid antigens and bacterial infection by using specific reagents for tracking these cells. Our results demonstrate dramaticin vivoexpansion and surface phenotype alterations after NKT cell activation with α-galactosylceramide. In addition, we show significant NK1.1 down-modulation on NKT cells in the setting of oralSalmonellainfection. Our results indicate thatin vivoactivation of NKT cells leads to a dynamic response characterized by surface receptor down-modulation and expansion. These findings alter current understanding of NKT cell biology and should aid in the rational design of NKT cell-based immunotherapies.

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