Renal carcinoma cell-derived exosomes induce human immortalized line of Jurkat T lymphocyte apoptosis in vitro.
OBJECTIVE
Tumor-derived exosomes usually contain some molecules that can help immune evasion by tumors. This study is aimed at investigating the potential effect of exosomes from human kidney adenocarcinoma cells on a human immortalized line of Jurkat T lymphocytes in vitro.


METHODS
Exosomes were purified from human kidney adenocarcinoma ACHN cells by sequential centrifugations and ultrafiltrations, and characterized by transmission electron microscopy. The effects of exosomes on the proliferation, cytokine production and apoptosis of Jurkat T cells were determined using flow cytometry and enzyme-linked immunosorbent assay. The relative levels of pro- and anti-apoptotic molecules were determined by Western blotting.


RESULTS
Exosomes were purified from ACHN cells and exhibited typical characteristics. Treatment with exosomes inhibited Jurkat T cell proliferation and induced Jurkat T cell apoptosis in a dose- and time-dependent manner. Treatment with exosomes reduced spontaneous interleukin-2 (IL-2), interferon-γ, IL-6 and IL-10 production by Jurkat T cells. Treatment with exosomes increased the relative levels of cleaved caspase-3, -8 and -9 as well as Bax, but reduced the levels of Bcl-2 in Jurkat T cells. The purified exosomes contained Fas ligand, and treatment with soluble Fas abrogated exosome-mediated Jurkat T cell apoptosis.


CONCLUSIONS
Our data indicate that exosomes from kidney adenocarcinoma cells contain Fas ligand and trigger Jurkat T cell apoptosis, contributing to the immune evasion of tumors.
Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.
Lin
L
Yang
Xiaohou
X
Wu
Dan
D
Wang
Chunli
C
Luo
Lixue
L
Chen
D000230:Adenocarcinoma / Q000378:metabolism*; D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019169:Jurkat Cells; D007680:Kidney Neoplasms / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016753:Interleukin-10; D007371:Interferon-gamma