Profound Enhancement of the IL-12/IL-18 Pathway of IFN-γ Secretion in Human CD8+ Memory T Cell Subsets via IL-15

作者: Ronald B. Smeltz

DOI: 10.4049/JIMMUNOL.178.8.4786

关键词:

摘要: Human memory CD8(+) T cell subsets, termed central and effector cells, can be identified by expression of CD45RA, CD62 ligand (CD62L), CCR7. Accordingly, functional differences have been described for each subset, reflecting unique roles in immunological memory. The common gamma-chain cytokines IL-15 IL-7 shown to induce proliferation differentiation human as well increased functions (i.e., cytokines, cytotoxicity). In this study, we observed that addition or cultures cells profoundly enhanced the IL-12-IL-18 pathway IFN-gamma production. Importantly, lowered threshold concentrations IL-12 IL-18 required induction 100-fold. Comparison demonstrated was superior its ability enhance IL-12-IL-18-induced IFN-gamma, without evidence a synergistic effect between IL-7. We also IL-15- IL-7-mediated enhancement production property cells. Despite lack association division acquisition down-regulation CD62L correlated with IFN-gamma. Purified stimulated down-regulated acquired potent similar Thus, known role development memory, may amplify increasing sensitivity proinflammatory cytokine stimulation.

参考文章(39)
Kazuko Uno, Yoko Mitsuishi, Mari Tanigawa, Kiyotaka Okuno, Norihiko Hirai, Youichi Mizutani, Hideo Saotome, Hiromi Fujiwara, Tsunataro Kishida, A series of immune responses leading to the induction ofT cell IL-12/IL-18 responsiveness in patientswith relatively large tumor burdens Cancer Immunology, Immunotherapy. ,vol. 52, pp. 33- 40 ,(2003) , 10.1007/S00262-002-0329-8
Kimberly S. Schluns, Kristina Williams, Averil Ma, Xin X. Zheng, Leo Lefrançois, Cutting Edge: Requirement for IL-15 in the Generation of Primary and Memory Antigen-Specific CD8 T Cells Journal of Immunology. ,vol. 168, pp. 4827- 4831 ,(2002) , 10.4049/JIMMUNOL.168.10.4827
Taku Kambayashi, Erika Assarsson, Aron E. Lukacher, Hans-Gustaf Ljunggren, Peter E. Jensen, Memory CD8+T Cells Provide an Early Source of IFN-γ The Journal of Immunology. ,vol. 170, pp. 2399- 2408 ,(2003) , 10.4049/JIMMUNOL.170.5.2399
Todd A. Fehniger, Haixin Yu, Megan A. Cooper, Kazuhiro Suzuki, Manisha H. Shah, Michael A. Caligiuri, Cutting Edge: IL-15 Costimulates the Generalized Shwartzman Reaction and Innate Immune IFN-γ Production In Vivo The Journal of Immunology. ,vol. 164, pp. 1643- 1647 ,(2000) , 10.4049/JIMMUNOL.164.4.1643
Ester M. van Leeuwen, Laila E. Gamadia, Paul A. Baars, Ester B. Remmerswaal, Ineke J. ten Berge, René A. van Lier, Proliferation Requirements of Cytomegalovirus-Specific, Effector-Type Human CD8+ T Cells Journal of Immunology. ,vol. 169, pp. 5838- 5843 ,(2002) , 10.4049/JIMMUNOL.169.10.5838
Masashi Kurimoto, Steven Clark, Hyun-Jong Ahn, Xu-Yu Zhou, Jie Mu, Michio Tomura, Seiji Maruo, Hiromi Fujiwara, Haruki Okamura, Kenji Nakanishi, Toshiyuki Hamaoka, Differential capacities of CD4+, CD8+, and CD4-CD8- T cell subsets to express IL-18 receptor and produce IFN-gamma in response to IL-18. Journal of Immunology. ,vol. 160, pp. 3759- 3765 ,(1998)
K. Liu, M. Catalfamo, Y. Li, P. A. Henkart, N.-p. Weng, IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8+ memory T cells. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 6192- 6197 ,(2002) , 10.1073/PNAS.092675799
Lisa S. Berenson, Naruhisa Ota, Kenneth M. Murphy, Issues in T-helper 1 development--resolved and unresolved. Immunological Reviews. ,vol. 202, pp. 157- 174 ,(2004) , 10.1111/J.0105-2896.2004.00208.X
Rance E. Berg, Christoph J. Cordes, James Forman, Contribution of CD8+ T cells to innate immunity: IFN-γ secretion induced by IL-12 and IL-18 European Journal of Immunology. ,vol. 32, pp. 2807- 2816 ,(2002) , 10.1002/1521-4141(2002010)32:10<2807::AID-IMMU2807>3.0.CO;2-0
Federica Sallusto, Danielle Lenig, Reinhold Förster, Martin Lipp, Antonio Lanzavecchia, Two subsets of memory T lymphocytes with distinct homing potentials and effector functions Nature. ,vol. 401, pp. 708- 712 ,(1999) , 10.1038/44385