Abstract
Interleukin (IL)-15 has emerged as a key regulator of both natural killer (NK) cell differentiation and activation. The aim of the present study was to investigate the expansion of the population of cells expressing killer-cell immunoglobulin-like receptors (CD158a and CD158b) in human peripheral lymphocytes by treatment with IL-15. One million peripheral lymphocytes were cultured in RPMI1640 medium alone or in medium containing IL-2 at 100 U/ml or IL-15 at 0.1, 1.0, or 10.0 ng/ml for 48 h. After each incubation, we assessed the natural killing activity and the population of CD16(+)CD158a(+)/b(+) cells and CD8(+)CD158a(+)/b(+) cells. IL-15 increased the NK activity and expanded the populations of CD16(+)CD158a(+)/b(+) cells and CD8(+)CD158a(+)/b(+) cells. These actions were dose dependent, and the effects of IL-15 at 1.0 ng/ml were close to those of IL-2 at 100 U/ml. These findings suggest that IL-15 induces the effector functions of resting NK cells throughout the body, and thereby plays a critical role in the activation of tissue-associated immune responses.
Full Text
The Full Text of this article is available as a PDF (158.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Agostini C., Trentin L., Sancetta R., Facco M., Tassinari C., Cerutti A., Bortolin M., Milani A., Siviero M., Zambello R. Interleukin-15 triggers activation and growth of the CD8 T-cell pool in extravascular tissues of patients with acquired immunodeficiency syndrome. Blood. 1997 Aug 1;90(3):1115–1123. [PubMed] [Google Scholar]
- Armitage R. J., Macduff B. M., Eisenman J., Paxton R., Grabstein K. H. IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation. J Immunol. 1995 Jan 15;154(2):483–490. [PubMed] [Google Scholar]
- Binstadt B. A., Brumbaugh K. M., Dick C. J., Scharenberg A. M., Williams B. L., Colonna M., Lanier L. L., Kinet J. P., Abraham R. T., Leibson P. J. Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation. Immunity. 1996 Dec;5(6):629–638. doi: 10.1016/s1074-7613(00)80276-9. [DOI] [PubMed] [Google Scholar]
- Bulfone-Paus S., Ungureanu D., Pohl T., Lindner G., Paus R., Rückert R., Krause H., Kunzendorf U. Interleukin-15 protects from lethal apoptosis in vivo. Nat Med. 1997 Oct;3(10):1124–1128. doi: 10.1038/nm1097-1124. [DOI] [PubMed] [Google Scholar]
- Carson W. E., Fehniger T. A., Haldar S., Eckhert K., Lindemann M. J., Lai C. F., Croce C. M., Baumann H., Caligiuri M. A. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Invest. 1997 Mar 1;99(5):937–943. doi: 10.1172/JCI119258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carson W. E., Giri J. G., Lindemann M. J., Linett M. L., Ahdieh M., Paxton R., Anderson D., Eisenmann J., Grabstein K., Caligiuri M. A. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med. 1994 Oct 1;180(4):1395–1403. doi: 10.1084/jem.180.4.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colonna M., Samaridis J. Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. Science. 1995 Apr 21;268(5209):405–408. doi: 10.1126/science.7716543. [DOI] [PubMed] [Google Scholar]
- D'Andrea A., Chang C., Franz-Bacon K., McClanahan T., Phillips J. H., Lanier L. L. Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes. J Immunol. 1995 Sep 1;155(5):2306–2310. [PubMed] [Google Scholar]
- Dunne J., Lynch S., O'Farrelly C., Todryk S., Hegarty J. E., Feighery C., Doherty D. G. Selective expansion and partial activation of human NK cells and NK receptor-positive T cells by IL-2 and IL-15. J Immunol. 2001 Sep 15;167(6):3129–3138. doi: 10.4049/jimmunol.167.6.3129. [DOI] [PubMed] [Google Scholar]
- Frohn C., Schlenke P., Kirchner H. The repertoire of HLA-Cw-specific NK cell receptors CD158 a/b (EB6 and GL183) in individuals with different HLA phenotypes. Immunology. 1997 Dec;92(4):567–570. doi: 10.1046/j.1365-2567.1997.00374.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grabstein K. H., Eisenman J., Shanebeck K., Rauch C., Srinivasan S., Fung V., Beers C., Richardson J., Schoenborn M. A., Ahdieh M. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science. 1994 May 13;264(5161):965–968. doi: 10.1126/science.8178155. [DOI] [PubMed] [Google Scholar]
- Huard B., Karlsson L., Triebel F. KIR down-regulation on NK cells is associated with down-regulation of activating receptors and NK cell inactivation. Eur J Immunol. 2001 Jun;31(6):1728–1735. doi: 10.1002/1521-4141(200106)31:6<1728::aid-immu1728>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
- Kanegane H., Tosato G. Activation of naive and memory T cells by interleukin-15. Blood. 1996 Jul 1;88(1):230–235. [PubMed] [Google Scholar]
- Khan I. A., Kasper L. H. IL-15 augments CD8+ T cell-mediated immunity against Toxoplasma gondii infection in mice. J Immunol. 1996 Sep 1;157(5):2103–2108. [PubMed] [Google Scholar]
- Lanier L. L. NK cell receptors. Annu Rev Immunol. 1998;16:359–393. doi: 10.1146/annurev.immunol.16.1.359. [DOI] [PubMed] [Google Scholar]
- Lanier L. L., Phillips J. H. Inhibitory MHC class I receptors on NK cells and T cells. Immunol Today. 1996 Feb;17(2):86–91. doi: 10.1016/0167-5699(96)80585-8. [DOI] [PubMed] [Google Scholar]
- Lodolce J. P., Boone D. L., Chai S., Swain R. E., Dassopoulos T., Trettin S., Ma A. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity. 1998 Nov;9(5):669–676. doi: 10.1016/s1074-7613(00)80664-0. [DOI] [PubMed] [Google Scholar]
- McInnes I. B., al-Mughales J., Field M., Leung B. P., Huang F. P., Dixon R., Sturrock R. D., Wilkinson P. C., Liew F. Y. The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. Nat Med. 1996 Feb;2(2):175–182. doi: 10.1038/nm0296-175. [DOI] [PubMed] [Google Scholar]
- Moretta A., Poggi A., Pende D., Tripodi G., Orengo A. M., Pella N., Augugliaro R., Bottino C., Ciccone E., Moretta L. CD69-mediated pathway of lymphocyte activation: anti-CD69 monoclonal antibodies trigger the cytolytic activity of different lymphoid effector cells with the exception of cytolytic T lymphocytes expressing T cell receptor alpha/beta. J Exp Med. 1991 Dec 1;174(6):1393–1398. doi: 10.1084/jem.174.6.1393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moretta L., Ciccone E., Moretta A., Höglund P., Ohlén C., Kärre K. Allorecognition by NK cells: nonself or no self? Immunol Today. 1992 Aug;13(8):300–306. doi: 10.1016/0167-5699(92)90042-6. [DOI] [PubMed] [Google Scholar]
- Nakajima H., Cella M., Langen H., Friedlein A., Colonna M. Activating interactions in human NK cell recognition: the role of 2B4-CD48. Eur J Immunol. 1999 May;29(5):1676–1683. doi: 10.1002/(SICI)1521-4141(199905)29:05<1676::AID-IMMU1676>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
- Ogasawara K., Hida S., Azimi N., Tagaya Y., Sato T., Yokochi-Fukuda T., Waldmann T. A., Taniguchi T., Taki S. Requirement for IRF-1 in the microenvironment supporting development of natural killer cells. Nature. 1998 Feb 12;391(6668):700–703. doi: 10.1038/35636. [DOI] [PubMed] [Google Scholar]
- Puzanov I. J., Bennett M., Kumar V. IL-15 can substitute for the marrow microenvironment in the differentiation of natural killer cells. J Immunol. 1996 Nov 15;157(10):4282–4285. [PubMed] [Google Scholar]
- Vivier E., Daëron M. Immunoreceptor tyrosine-based inhibition motifs. Immunol Today. 1997 Jun;18(6):286–291. doi: 10.1016/s0167-5699(97)80025-4. [DOI] [PubMed] [Google Scholar]
- Wagtmann N., Biassoni R., Cantoni C., Verdiani S., Malnati M. S., Vitale M., Bottino C., Moretta L., Moretta A., Long E. O. Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. Immunity. 1995 May;2(5):439–449. doi: 10.1016/1074-7613(95)90025-x. [DOI] [PubMed] [Google Scholar]
- Warren H. S., Campbell A. J., Waldron J. C., Lanier L. L. Biphasic response of NK cells expressing both activating and inhibitory killer Ig-like receptors. Int Immunol. 2001 Aug;13(8):1043–1052. doi: 10.1093/intimm/13.8.1043. [DOI] [PubMed] [Google Scholar]
- Warren H. S., Kinnear B. F., Kastelein R. L., Lanier L. L. Analysis of the costimulatory role of IL-2 and IL-15 in initiating proliferation of resting (CD56dim) human NK cells. J Immunol. 1996 May 1;156(9):3254–3259. [PubMed] [Google Scholar]
- Yokoyama W. M., Seaman W. E. The Ly-49 and NKR-P1 gene families encoding lectin-like receptors on natural killer cells: the NK gene complex. Annu Rev Immunol. 1993;11:613–635. doi: 10.1146/annurev.iy.11.040193.003145. [DOI] [PubMed] [Google Scholar]
