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

J Immunol. 2008 Sep 1;181(5):3268-76. doi: 10.4049/jimmunol.181.5.3268.

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 display alloreactivity, for which they use mechanisms characteristic of both NK and conventional T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Antigen-Presenting Cells
  • Antigens, CD1 / metabolism*
  • Antigens, CD1d
  • Glycosphingolipids / metabolism
  • Humans
  • Isoantigens / immunology*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Protein Binding
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Immunologic / immunology*
  • T-Lymphocytes

Substances

  • Antigens, CD1
  • Antigens, CD1d
  • CD1D protein, human
  • Glycosphingolipids
  • Isoantigens
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic