演題詳細

一般口演 / Oral Session

一般口演 105 (Oral Session 105) :免疫制御

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日程
2013年10月13日(日)
時間
15:00 - 16:00
会場
第13会場 / Room No.13 (札幌市教育文化会館 3F 研修室301)
座長・司会
渋谷 彰 (Akira Shibuya):1
1:筑波大学医学医療系 免疫学
 
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K562 based artificial antigen presenting cells inhibit T cell proliferation

演題番号 : OS-3-171

谷本 一史 (Kazushi Tanimoto):1,2、藤原 弘 (Hiroshi Fujiwara):1、Pawel Muranski:2、John A. Barrett:2、Joseph J. Melenhorst:3

1:Dept. Hematology, Clinical Immunology and Infectious Diseases, Ehime Univ., Japan、2:Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA、3:Abramson Cancer Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

 

The human leukemia cell line K562 represents an attractive platform for an artificial antigen presenting cell (aAPC): it is readily expandable, does not express HLA molecules, and can be stably transduced with various genes. To generate an aAPC to expand CMV-specific T cells for adoptive immunotherapy, we transduced K562 with HLA-A2 in combination with 4-1BBL, or CD64, or HLA-DR15. In preliminary experiments, irradiated aAPC pulsed with CMV peptides failed to elicit antigen-specific T cells. Then we found that both wildtype K562 and K562 based aAPC strongly inhibited T cell proliferation to the SEB, OKT3, and in MLR. The result of transwell experiments indicated that suppression was mediated by a soluble factor. MLR inhibition was not reversed by TGFβ blocking or PGE2 inhibitors. Finally, the full abrogation of the suppression of K562 was achieved by a brief fixation of cells with low concentration of formaldehyde. The MLR and T cell response to SEB- and OKT3-loaded aAPC were restored when using fixed K562. Moreover, fixed, CMV peptides pulsed aAPC induced robust expansion of CMV-specific T cells when compared with irradiated aAPC. Thus, fixed K562 cell constructs efficiently presented antigen and stimulated T cells. Here we demonstrate that K562 can serve as a source of aAPC for cell therapy approaches after abrogation of their suppressive activity using formaldehyde. Our result suggested that K562 displays myeloid-derived suppressor cell-like functionality, and these findings have implications for understanding of the immune evasion mechanisms of leukemia.

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