IL-15/IL-15 receptor biology: A guided tour through an expanding universe

Budagian, Vadim; Bulanova, Elena; Paus, Ralf; Bulfone–Paus∥, Silvia

doi:10.1016/j.cytogfr.2006.05.001

Cited by 329 publications

(357 citation statements)

References 207 publications

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“…6 IL-15 is essential for the development and function of NK cells. 7 Coculture of NK cells with K562 cells ectopically coexpressing 4-1BB ligand (4-1BBL) and membrane-bound IL-15 effectively promotes the expansion of NK cells in vitro and mediates their cytotoxicity against some leukemia cells. 8,9 In addition, IL-15 upregulates the expression of NKG2D on NK and T cells, even in the presence of soluble NKG2DL.…”

Section: Introductionmentioning

confidence: 99%

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Gong

Xiao

et al. 2010

Cell Mol Immunol

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Major histocompatibility complex (MHC) class I chain-related protein A (MICA), which is a ligand for human NKG2D, is expressed by a variety of epithelial tumor cells and promotes the activation of natural killer (NK), CD8 1 and cd-T cells. Although ectopic expression of MICA on tumor cells elicits anti-tumor responses, soluble MICA downregulates the activities of lymphocytes. In this study, we showed that recombinant, immobilized MICA (iMICA) molecules coated on plastic wells weakly promote peripheral NK cell activation, secretion of interferon (IFN)-c and degranulation without inducing apoptosis. In addition, iMICA synergized with IL-15 and soluble 4-1BB ligand (s4-1BBL) to expand NK cells 25-to 42-fold in a 13-day culture, whereas NK cells stimulated only with IL-15 and s4-1BBL expanded 10-to 16-fold. In contrast to NK cells expanded by IL-15 and s4-1BBL stimulation, NK cells expanded long term in the presence of iMICA exhibited increased cytotoxicity against leukemia cells. These results suggest that large numbers of NK cells with high cytotoxicity can be generated by stimulation with IL-15 and s4-1BBL in the presence of iMICA and that these cells can be used for adoptive cancer immunotherapy. Studies on the 4-1BB signaling pathway have shown that ligation of 4-1BB promotes the survival and multiplication of CD8 1 T and NK cells. 6 IL-15 is essential for the development and function of NK cells. 7 Coculture of NK cells with K562 cells ectopically coexpressing 4-1BB ligand (4-1BBL) and membrane-bound IL-15 effectively promotes the expansion of NK cells in vitro and mediates their cytotoxicity against some leukemia cells. 8,9 In addition, IL-15 upregulates the expression of NKG2D on NK and T cells, even in the presence of soluble NKG2DL. 10 IL-15 and NKG2D signals cross-regulate each other and

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Section: Introductionmentioning

confidence: 99%

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Gong

Xiao

et al. 2010

Cell Mol Immunol

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“…[8][9][10] For some of these authors, IKDCs may represent an activated status of conventional NK cells. 8 IL-15 11,12 is an absolutely essential cytokine for the differentiation and maintenance of memory CD8 + T, NKT and NK cells. 13 IL-15 shows a broad tissue distribution at the mRNA level, but post-transcriptional and intracellular trafficking mechanisms confine functional production mainly to myeloid cells.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

et al. 2008

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“…I nterleukin-15 (IL-15) is a member of the four ␣-helix family of cytokines and has diverse roles in lymphocyte development, homeostasis, and activation (1)(2)(3). Both IL-15-and IL-15 receptor ␣ (IL-15R␣) 3 -deficient mice have similar phenotypes consisting of severe defects in the development of NK, NK T cells, and intraepithelial lymphocytes, as well as a lack of peripheral memory phenotype (MP) CD8 ϩ T cells (4,5).…”

mentioning

confidence: 99%

IL-15 Transpresentation Augments CD8+ T Cell Activation and Is Required for Optimal Recall Responses by Central Memory CD8+ T Cells

Kokaji

Hockley

Kane

2008

The Journal of Immunology

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Although the adaptive immune system has a remarkable ability to mount rapid recall responses to previously encountered pathogens, the cellular and molecular signals necessary for memory CD8+ T cell reactivation are poorly defined. IL-15 plays a critical role in memory CD8+ T cell survival; however, whether IL-15 is also involved in memory CD8+ T cell reactivation is presently unclear. Using artificial Ag-presenting surfaces prepared on cell-sized microspheres, we specifically addressed the role of IL-15 transpresentation on mouse CD8+ T cell activation in the complete absence of additional stimulatory signals. In this study we demonstrate that transpresented IL-15 is significantly more effective than soluble IL-15 in augmenting anti-CD3ε-induced proliferation and effector molecule expression by CD8+ T cells. Importantly, IL-15 transpresentation and TCR ligation by anti-CD3ε or peptide MHC complexes exhibited synergism in stimulating CD8+ T cell responses. In agreement with previous studies, we found that transpresented IL-15 preferentially stimulated memory phenotype CD8+ T cells; however, in pursuing this further, we found that central memory (TCM) and effector memory (TEM) CD8+ T cells responded differentially to transpresented IL-15. TCM CD8+ T cells undergo Ag-independent proliferation in response to transpresented IL-15 alone, whereas TEM CD8+ T cells are relatively unresponsive to transpresented IL-15. Furthermore, upon Ag-specific stimulation, TCM CD8+ T cell responses are enhanced by IL-15 transpresentation, whereas TEM CD8+ T cell responses are only slightly affected, both in vitro and in vivo. Thus, our findings distinguish the role of IL-15 transpresentation in the stimulation of distinct memory CD8+ T cell subsets, and they also have implications for ex vivo reactivation and expansion of Ag-experienced CD8+ T cells for immunotherapeutic approaches.

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IL-15/IL-15 receptor biology: A guided tour through an expanding universe

Cited by 329 publications

References 207 publications

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Immobilized MHC class I chain-related protein A synergizes with IL-15 and soluble 4-1BB ligand to expand NK cells with high cytotoxicity ex vivo

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

IL-15 Transpresentation Augments CD8+ T Cell Activation and Is Required for Optimal Recall Responses by Central Memory CD8+ T Cells

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