- Natural killer cells
- Natural killer subpopulations
- Scavenger receptor
The CD6 scavenger receptor is known to be expressed on virtually all T cells and is supposed to be involved in costimulation, synapse formation, thymic selection and leukocyte migration. Here, we demonstrate that CD6 is differentially expressed by a subpopulation of peripheral CD56dim natu- ral killer (NK) cells and absent on CD56bright NK cells. CD56dimCD16+ cells represent the major NK subset in the periphery, and most cells within this group are positive for CD6. Most killer immunoglobulin-like receptor- and immunoglobulin-like transcript-positive cells also belong to the CD6+ subpopulation, as expected from their restricted expression on CD56dim NK cells. In addition, CD6+ NK cells are similar to the newly identified CD94lowCD56dim NK subpopulation and most distant from the recently defined CD27+ NK subpopulation based on the reverse correlation of expression between CD6 and CD27, a marker associated primarily with CD56bright NK cells. With respect to CD6 function on NK cells, direct CD6 triggering did not result in degranulation but induced secretion of cytokines (interferon-γ and tumor necrosis factor-α) and chemokines [CXCL10 (IP-10), CXCL1 (GRO-α)]. Thus, CD6 expression on peripheral NK cells marks a novel CD56dim subpopulation associated with distinct patterns of cytokine and chemokine secretion.
Copyright © 2010 S. Karger AG, Basel
- Gregoire C, Chasson L, Luci C, Tomasello E, Geissmann F, Vivier E, Walzer T: The trafficking of natural killer cells. Immunol Rev 2007;220:169–182.
- Cooper MA, Fehniger TA, Caligiuri MA: The biology of human natural killer-cell subsets. Trends Immunol 2001;22:633–640.
- Anfossi N, Andre P, Guia S, Falk CS, Roetynck S, Stewart CA, Breso V, Frassati C, Reviron D, Middleton D, Romagne F, Ugolini S, Vivier E: Human NK cell education by inhibitory receptors for MHC class I. Immunity 2006;25:331–342.
- Chan A, Hong DL, Atzberger A, Kollnberger S, Filer AD, Buckley CD, McMichael A, Enver T, Bowness P: CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts. J Immunol 2007;179:89–94.
- Romagnani C, Juelke K, Falco M, Morandi B, D’Agostino A, Costa R, Ratto G, Forte G, Carrega P, Lui G, Conte R, Strowig T, Moretta A, Munz C, Thiel A, Moretta L, Ferlazzo G: CD56brightCD16– killer Ig-like receptor-NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation. J Immunol 2007;178:4947–4955.
- Loza MJ, Perussia B: The IL-12 signature: NK cell terminal CD56+high stage and effector functions. J Immunol 2004;172:88–96.
- Yu J, Mao HC, Wei M, Hughes T, Zhang J, Park IK, Liu S, McClory S, Marcucci G, Trotta R, Caligiuri MA: CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK cell subsets. Blood 2010;115:274–281.
- Singer NG, Richardson BC, Powers D, Hooper F, Lialios F, Endres J, Bott CM, Fox DA: Role of the CD6 glycoprotein in antigen-specific and autoreactive responses of cloned human T lymphocytes. Immunology 1996;88:537–543.
- Aruffo A, Bowen MA, Patel DD, Haynes BF, Starling GC, Gebe JA, Bajorath J: CD6-ligand interactions: a paradigm for SRCR domain function? Immunol Today 1997;18:498–504.
- Koopman LA, Kopcow HD, Rybalov B, Boyson JE, Orange JS, Schatz F, Masch R, Lockwood CJ, Schachter AD, Park PJ, Strominger JL: Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential. J Exp Med 2003;198:1201–1212.
- Vossen MT, Matmati M, Hertoghs KM, Baars PA, Gent MR, Leclercq G, Hamann J, Kuijpers TW, van Lier RA: CD27 defines phenotypically and functionally different human NK cell subsets. J Immunol 2008;180:3739–3745.
- Frey M, Packianathan NB, Fehniger TA, Ross ME, Wang WC, Stewart CC, Caligiuri MA, Evans SS: Differential expression and function of l-selectin on CD56bright and CD56dim natural killer cell subsets. J Immunol 1998;161:400–408.
- Juelke K, Killig M, Luetke-Eversloh M, Parente E, Gruen J, Morandi B, Ferlazzo G, Thiel A, Schmitt-Knosalla I, Romagnani C: CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells. Blood 2010;116:1299–1307.
- Ulbrecht M, Maier S, Hofmeister V, Falk CS, Brooks AG, McMaster MT, Weiss EH: Truncated HLA-G isoforms are retained in the endoplasmic reticulum and insufficiently provide HLA-E ligands. Hum Immunol 2004;65:200–208.
- Falk CS, Mach M, Schendel DJ, Weiss EH, Hilgert I, Hahn G: NK cell activity during human cytomegalovirus infection is dominated by US2-11-mediated HLA class I down-regulation. J Immunol 2002;169:3257–3266.
- von Geldern M, Simm B, Braun M, Weiss EH, Schendel DJ, Falk CS: TCR-independent cytokine stimulation induces non-MHC-restricted T cell activity and is negatively regulated by HLA class I. Eur J Immunol 2006;36:2347–2358.
- Lebbink RJ, de Ruiter T, Adelmeijer J, Brenkman AB, van Helvoort JM, Koch M, Farndale RW, Lisman T, Sonnenberg A, Lenting PJ, Meyaard L: Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1. J Exp Med 2006;203:1419–1425.
- Vitale M, Bottino C, Sivori S, Sanseverino L, Castriconi R, Marcenaro E, Augugliaro R, Moretta L, Moretta A: NKP44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis. J Exp Med 1998;187:2065–2072.
- Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L: Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 2001;19:197–223.
- Lopez-Verges S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, Norris PJ, Nixon DF, Lanier LL: CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK cell subset. Blood 2010;116:3865–3874.
- Bjorkstrom NK, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson MA, Bjorklund AT, Flodstrom-Tullberg M, Michaelsson J, Rottenberg ME, Guzman CA, Ljunggren HG, Malmberg KJ: Expression patterns of NKG2a, KIR, and CD57 define a process of CD56dim NK cell differentiation uncoupled from NK cell education. Blood 2010;116:3853–3864.
- Castro MA, Oliveira MI, Nunes RJ, Fabre S, Barbosa R, Peixoto A, Brown MH, Parnes JR, Bismuth G, Moreira A, Rocha B, Carmo AM: Extracellular isoforms of CD6 generated by alternative splicing regulate targeting of CD6 to the immunological synapse. J Immunol 2007;178:4351–4361.
- Bowen MA, Whitney GS, Neubauer M, Starling GC, Palmer D, Zhang J, Nowak NJ, Shows TB, Aruffo A: Structure and chromosomal location of the human CD6 gene: detection of five human CD6 isoforms. J Immunol 1997;158:1149–1156.
- Alonso R, Huerta V, de Leon J, Piedra P, Puchades Y, Guirola O, Chinea G, Montero E: Towards the definition of a chimpanzee and human conserved CD6 domain 1 epitope recognized by T1 monoclonal antibody. Hybridoma (Larchmt) 2008;27:291–301.
- Cayrol R, Wosik K, Berard JL, Dodelet- Devillers A, Ifergan I, Kebir H, Haqqani AS, Kreymborg K, Krug S, Moumdjian R, Bouthillier A, Becher B, Arbour N, David S, Stanimirovic D, Prat A: Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol 2008;9:137–145.
- Valiante NM, Uhrberg M, Shilling HG, Lienert-Weidenbach K, Arnett KL, D’Andrea A, Phillips JH, Lanier LL, Parham P: Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity 1997;7:739–751.
- Rosshart S, Hofmann M, Schweier O, Pfaff AK, Yoshimoto K, Takeuchi T, Molnar E, Schamel WW, Pircher H: Interaction of KLRG1 with E-cadherin: new functional and structural insights. Eur J Immunol 2008;38:3354–3364.
- Nagler A, Lanier LL, Cwirla S, Phillips JH: Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol 1989;143:3183–3191.
- Braud VM, Allan DS, O’Callaghan CA, Soderstrom K, D’Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ: HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1998;391:795–799.
Prof. Dr. rer. nat. Christine S. Falk
Department of Transplantation Immunology, IFB-Tx
Medizinische Hochschule Hannover MHH
Carl-Neuberg-Strasse 1, DE–30625 Hannover (Germany)
Tel. +49 511 532 9745, Fax +49 511 532 8044, E-Mail email@example.com
Received: April 13, 2010
Accepted after revision: November 14, 2010
Published online: December 18, 2010
Number of Print Pages : 15
Number of Figures : 5, Number of Tables : 0, Number of References : 29
Journal of Innate Immunity
Vol. 3, No. 4, Year 2011 (Cover Date: June 2011)
Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)
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