Ly49 C/I-dependent NKT cell-derived IL-10 is required for corneal graft survival and peripheral tolerance

Journal of Leukocyte Biology
C M WatteJoan Stein-Streilein

Abstract

Similar to their activity on NK cells, Ly49 molecules play a pivotal role in influencing how NKT cells respond. It is known that Ly49 C/I is an inhibitory receptor capable of down-modulating proliferation, IFN-gamma response, and cytotoxic activity in cells that express it. In a model of peripheral tolerance induced via the eye, we observed that Ly49 C/I-positive, invariant NKT cells were required. To test if the NK inhibitory receptor functionally contributed to tolerance development, we used blocking antibody, in vivo and in vitro, to interfere with the development of antigen-specific suppression. A result of blocking ligation of Ly49 C/I inhibitory receptor prevented NKT cell production of IL-10 and the subsequent development of tolerance. Ly49 C/I-blocking antibodies also prevented corneal graft survival, a phenomenon dependent on eye-induced tolerance. Furthermore, in the presence of TCR stimulation, cross-linking of Ly49 C/I on CD4(+) NKT cells stimulated an increase in IL-10 mRNA and a decrease in IFN-gamma. The concept of Ly49 inhibitory receptors regulating immune reactivity to self by regulating immune activity of individual cells is thus expanded to include a role for the inhibitory receptors in the more global proce...Continue Reading

Citations

Oct 10, 2013·Mucosal Immunology·C Paget, F Trottein
Jan 5, 2011·Immunological Reviews·Purnima BhatGraham R Leggatt
Oct 8, 2008·Trends in Immunology·Joan Stein-Streilein
Sep 1, 2008·Expert Review of Clinical Immunology·Nadir KadriSusanna L Cardell
Dec 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen R MattarolloIan H Frazer
Mar 11, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiao-Tang YinPatrick M Stuart
Oct 30, 2018·Frontiers in Immunology·Filippo CortesiPaolo Dellabona

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