Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors

The Journal of Immunology : Official Journal of the American Association of Immunologists
Scott PattersonAnastasios Karadimitris

Abstract

Invariant NKT (iNKT) cells are a subset of highly conserved immunoregulatory T cells that modify a variety of immune responses, including alloreactivity. Central to their function is the interaction of the invariant TCR with glycosphingolipid (GSL) ligands presented by the nonpolymorphic MHC class I molecule CD1d and their ability to secrete rapidly large amounts of immunomodulatory cytokines when activated. Whether iNKT cells, like NK and conventional T cells, can directly display alloreactivity is not known. We show in this study that human iNKT cells and APC can establish a direct cross-talk leading to preferential maturation of allogeneic APC and a considerably higher reactivity of iNKT cells cultured with allogeneic rather that autologous APC. Although the allogeneic activation of iNKT cells is invariant TCR-CD1d interaction-dependent, GSL profiling suggests it does not involve the recognition of disparate CD1d/GSL complexes. Instead, we show that contrary to previous reports, iNKT cells, like NK and T cells, express killer Ig receptors at a frequency similar to that of conventional T cells and that iNKT cell allogeneic activation requires up-regulation and function of activating killer Ig receptors. Thus, iNKT cells can d...Continue Reading

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Citations

Mar 18, 2016·Transplantation·Arash MemarnejadianS M Mansour Haeryfar
Mar 13, 2010·Nature Reviews. Immunology·Laurent Gapin
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May 5, 2017·British Journal of Pharmacology·Tin KyawAlex Bobik
Jun 4, 2020·International Journal of Molecular Sciences·Angélica Díaz-BasabeFederica Facciotti

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