DENDRITIC CELLS REGULATE THE INDUCTION OF EFFECTOR AND MEMORY CD8+ T CELLS

作者: Erik Berk

DOI:

关键词: Regulatory T cellIL-2 receptorCytotoxic T cellCell biologyT cellAntigen-presenting cellImmunologyCD40Interleukin 21BiologyNatural killer T cell

摘要: Dendritic cells (DCs) are key antigen-presenting in the immune system that can induce pathogen-specific T cell responses by presenting antigen (signal 1) to antigen-specific combination with co-stimulatory/inhibitory molecules 2) and secretion of cytokines 3). The ability DCs orchestrate CD8+ responses, combined generate high numbers vitro allows for their use DC-based vaccination protocols. success protocols other forms immunotherapy cancer is believed depend on successful induction both effector (CTLs), able migrate into kill tumors, long-lived memory cells, a secondary response upon tumor recurrence. However, signals drive differentiation each these subsets role this respect remain unclear. Studies have suggested same DC early after maturation while inducing prolonged when become exhausted. Here, I analyzed matured under conditions mimicking acute/early inflammation (“inflammatory-DCs”) or chronic/late (“non-inflammatory-DCs”) cells. observed “inflammatory-DCs” produce levels IL-12p70 naive cytolytic peripheral homing ability. Furthermore, demonstrate process. In contrast, “non-inflammatory-DCs” (exhausted DCs) do not direct central-memory superior anti-tumor guided me develop an alternative, low-cost method generating strong CTL Lastly, show modulation tumor-chemokine environment IFN, poly-I:C indomethacin enhanced attraction tumor-specific CTLs reducing regulatory attraction. Together, presented data broadens our understanding mechanisms DC-induced might lead improved vaccines.

参考文章(58)
Paweł Kaliński, Catharien M. U. Hilkens, Alies Snijders, Frank G. M. Snijdewint, Martien L. Kapsenberg, Dendritic cells, obtained from peripheral blood precursors in the presence of PGE2, promote Th2 responses Advances in Experimental Medicine and Biology. ,vol. 417, pp. 363- 367 ,(1997) , 10.1007/978-1-4757-9966-8_59
Anja Langenkamp, Mara Messi, Antonio Lanzavecchia, Federica Sallusto, Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nature Immunology. ,vol. 1, pp. 311- 316 ,(2000) , 10.1038/79758
Marina Cella, David Jarrossay, Fabio Facchetti, Olga Alebardi, Hideo Nakajima, Antonio Lanzavecchia, Marco Colonna, Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nature Medicine. ,vol. 5, pp. 919- 923 ,(1999) , 10.1038/11360
Pedro L. Vieira, Esther C. de Jong, Eddy A. Wierenga, Martien L. Kapsenberg, Paweł Kaliński, Development of Th1-Inducing Capacity in Myeloid Dendritic Cells Requires Environmental Instruction Journal of Immunology. ,vol. 164, pp. 4507- 4512 ,(2000) , 10.4049/JIMMUNOL.164.9.4507
Toshimichi Matsui, John E. Connolly, Mark Michnevitz, Damien Chaussabel, Chun-I Yu, Casey Glaser, Sasha Tindle, Marc Pypaert, Heidi Freitas, Bernard Piqueras, Jacques Banchereau, A. Karolina Palucka, CD2 Distinguishes Two Subsets of Human Plasmacytoid Dendritic Cells with Distinct Phenotype and Functions The Journal of Immunology. ,vol. 182, pp. 6815- 6823 ,(2009) , 10.4049/JIMMUNOL.0802008
Eugene Maraskovsky, Elizabeth Daro, Eileen Roux, Mark Teepe, Charlie R. Maliszewski, Jeannie Hoek, Dania Caron, Mel E. Lebsack, Hilary J. McKenna, In vivo generation of human dendritic cell subsets by Flt3 ligand Blood. ,vol. 96, pp. 878- 884 ,(2000) , 10.1182/BLOOD.V96.3.878
Fabio Re, Jack L. Strominger, Toll-like receptor 2 (TLR2) and TLR4 differentially activate human dendritic cells. Journal of Biological Chemistry. ,vol. 276, pp. 37692- 37699 ,(2001) , 10.1074/JBC.M105927200
Kristin V. Tarbell, Sayuri Yamazaki, Kara Olson, Priscilla Toy, Ralph M. Steinman, CD25+ CD4+ T Cells, Expanded with Dendritic Cells Presenting a Single Autoantigenic Peptide, Suppress Autoimmune Diabetes Journal of Experimental Medicine. ,vol. 199, pp. 1467- 1477 ,(2004) , 10.1084/JEM.20040180
Matthias Bros, Frank Jährling, Andrea Renzing, Nadine Wiechmann, Ngoc-Anh Dang, Arne Sutter, Ralf Ross, Jürgen Knop, Stephan Sudowe, Angelika B. Reske-Kunz, A newly established murine immature dendritic cell line can be differentiated into a mature state, but exerts tolerogenic function upon maturation in the presence of glucocorticoid Blood. ,vol. 109, pp. 3820- 3829 ,(2007) , 10.1182/BLOOD-2006-07-035576