The ex vivo microenviroments in MLTC of poorly immunogenic tumor cells facilitate polarization of CD4+CD25+ regulatory T cells.
CD4+CD25+ regulatory T (TR) cells play an important role in maintaining a balanced peripheral immune system. Recent studies have shown that TR cells may also play a key role in suppressing anti-tumor immune response. In order to investigate the tumor immune microenvironment and its influence on TR polarization, poorly immunogenic tumor cell line D5 (C57BL/6, H-2b), immunogenic tumor cell lines FBL3 (C57BL/6, H-2b) and H22 BALB/c, H-2d) were used to establish the syngeneic/allogeneic, poorly immunogenic/immunogenic mixed lymphocytes-tumor cell culture (MLTC). Our results revealed that the proportion of CD4+CD25+ T cells in MLTC of syngeneic primed splenocytes stimulated with D5 tumor cells was higher than that with H22 cells (0.43% vs 0.044%, and the similar results appeared in allogeneic splenocytes stimulated with D5 tumor cells (0.39% vs 0.04%). The splenocytes stimulated with supernatant from syngeneic MLTC of D5 tumor cells demonstrated higher proportion of CD4+CD25+ cells than that from allogeneic MLTC of D5 tumor cells, and the splenocytes stimulated with supernatant from syngeneic or allogeneic MLTC of H22 tumor cells generated lower proportion of CD4+CD25+ T cells than that of D5 tumor cells. The TGF-beta1 and Th2-oriented cytokines (IL-4 and IL-10) were dominated in supernatants of syngeneic MLTC of poorly immunogenic tumor cells. Our results provided useful information for studying the mechanisms underlying tumor immune surveillance as well as for the tumor immunotherapy.
Wang
Yan
Y
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute for Cancer Research at Medical Campus, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710061, China.
Zhou
Le
L
Wang
Hong Yan
HY
Xiao
Ju Xiang
JX
Si
Lu Sheng
LS
Wang
Yi Li
YL
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
D015704:CD4 Antigens; D015375:Receptors, Interleukin-2; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D015847:Interleukin-4