Human invariant NKT cells display alloreactivity instructed by invariant TCR-CD1d interaction and killer Ig receptors.
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.
Patterson
Scott
S
Department of Hematology, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.
Chaidos
Aristeidis
A
Neville
David C A
DC
Poggi
Alessandro
A
Butters
Terry D
TD
Roberts
Irene A G
IA
Karadimitris
Anastasios
A
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D006028:Glycosphingolipids; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic