Antigen-induced tolerance by intrathymic modulation of self-recognizing inhibitory receptors.
CD1d-restricted invariant natural killer T cell (iNKT cells) have a limited T cell receptor (TCR) repertoire and share characteristics common to T cells and natural killer cells. While intrathymic selection facilitates the production of T cells carrying self major histocompatibility complex-restricted TCRs, natural killer cells carry an appropriate repertoire of self major histocompatibility complex-recognizing receptors to avoid self-reactivity. Here we show that chronic exposure to specific glycolipid antigen resulted in iNKT cell disappearance and thymus-dependent repopulation of iNKT cells with increased expression of inhibitory Ly-49 molecules that resulted in impaired responsiveness. Thymic selection of peripheral Ly-49-expressing iNKT cell repertoire inhibited cytokine production and other functions in vivo. These observations emphasize the acquisition of self-recognizing inhibitory receptors on NKT cells as a previously unknown mechanism of thymic tolerance after chronic antigen exposure.
Hayakawa
Yoshihiro
Y
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria 3002, Australia. yoshihiro.hayakawa@petermac.org
Berzins
Stuart P
SP
Crowe
Nadine Y
NY
Godfrey
Dale I
DI
Smyth
Mark J
MJ
D000818:Animals; D000941:Antigens / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000378:metabolism; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
D000941:Antigens; D006017:Glycolipids; D018160:Receptors, Cytoplasmic and Nuclear