Transpresentation has emerged as an important mechanism mediating IL-15 responses in a subset of lymphocytes during the steady state. In transpresentation, cell surface IL-15, bound to IL-15Rα is delivered to opposing lymphocytes during a cell-cell interaction. The events most dependent on IL-15 include the development and homeostasis of memory CD8 T cells, Natural Killer cells, invariant Natural Killer T cells, and intraepithelial lymphocytes. As lymphocyte development and homeostasis involve multiple steps and mechanisms, IL-15 transpresentation can have diverse roles throughout. Moreover, distinct stages of lymphocyte differentiation require IL-15 transpresented by different cells, which include both hematopoietic and non-hematopoietic cell types. Herein, we will describe the points where IL-15 transpresentation impacts these processes, the specific cells thought to drive IL-15 responses, as well as their role in the course of development and homeostasis.
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http://dx.doi.org/10.1016/j.cyto.2012.06.017 | DOI Listing |
J Am Chem Soc
November 2024
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Protein complexes are crucial structures that control many biological processes. Harnessing these structures could be valuable for therapeutic therapy. However, their instability and short lifespans need to be addressed for effective use.
View Article and Find Full Text PDFJ Immunol
November 2024
Department of Immunobiology, Yale School of Medicine, New Haven, CT.
Expression of IL-15 on the surface of human graft endothelial cells (ECs) bound to the IL-15Rα subunit can increase the activation of CTLs, potentiating allograft rejection. Our previous work showed that surface expression of this protein complex could be induced by alloantibody-mediated complement activation through increased IL-1β synthesis, secretion, and autocrine/paracrine IL-1-mediated activation of NF-κB. In this article, we report that cultured human ECs express eight differently spliced IL-15 transcripts.
View Article and Find Full Text PDFAnticancer Agents Med Chem
October 2024
Graduate School of Education, Shandong Sport University, Jinan, 250102, China.
Front Immunol
June 2024
Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Background: Inflammatory cytokines play key pathogenic roles in liver fibrosis. IL-15 is a proinflammatory cytokine produced by myeloid cells. IL-15 promotes pathogenesis of several chronic inflammatory diseases.
View Article and Find Full Text PDFSci Transl Med
March 2024
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany.
Despite the advances in cancer treatment achieved, for example, by the CD20 antibody rituximab, an urgent medical need remains to optimize the capacity of such antibodies to induce antibody-dependent cellular cytotoxicity (ADCC) that determines therapeutic efficacy. The cytokine IL-15 stimulates proliferation, activation, and cytolytic capacity of NK cells, but broad clinical use is prevented by short half-life, poor accumulation at the tumor site, and severe toxicity due to unspecific immune activation. We here report modified immunocytokines consisting of Fc-optimized CD19 and CD20 antibodies fused to an IL-15 moiety comprising an L45E-E46K double mutation (MIC format).
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