Low molecular weight fraction secreted by SKOV3 cells expands peripheral CD4+CD25+ regulatory T cells and enhances their suppressive capacity.
The increase of CD4+CD25+ regulatory T cells in patients with ovarian carcinoma has been verified. Here we investigated the effects of supernatant derived from ovarian carcinoma cell SKOV3 on peripheral regulatory T cells. Supernatant from SKOV3 was collected and fractionated into three different molecular weight fractions (MWFs). The proliferation of the CD4+CD25+ regulatory T cells cultured in complete RPMI 1640 medium with the different stimulators was detected. The phenotype (GITR and CTLA-4) of natural and expanded CD4+CD25+ T cells was detected by flow cytometry. Foxp3 mRNA expression of low MWF-expanded CD4+CD25+ T cells was detected by RT-PCR. Those expanded CD4+CD25+ regulatory T cells showed enhanced capacity to suppress CD4+CD25- T proliferation and increased expression of GITR and CTLA-4. In brief, low molecular weight fraction of supernatant secreted by SKOV3 could expand peripheral CD4+CD25+ regulatory T cells and enhance their suppressive function.
Li
Xiao
X
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China. lixsure@yahoo.com.cn
Wan
Xiaoyun
X
Mao
Yuyan
Y
Lu
Weiguo
W
Xie
Xing
X
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D005591:Chemical Fractionation; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D015703:Antigens, CD; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D017077:Culture Media, Conditioned; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human