Low molecular weight fraction secreted by SKOV3 cells expands peripheral CD4+CD25+ regulatory T cells and enhances their suppressive capacity

Med Oncol. 2010 Sep;27(3):600-6. doi: 10.1007/s12032-009-9255-3. Epub 2009 Jun 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • CD4 Antigens / analysis
  • CTLA-4 Antigen
  • Carcinoma / metabolism*
  • Cell Line, Tumor / metabolism
  • Cells, Cultured / drug effects
  • Chemical Fractionation
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology*
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Neoplastic
  • Glucocorticoid-Induced TNFR-Related Protein
  • Humans
  • Immune Tolerance / drug effects*
  • Immunophenotyping
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Molecular Weight
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Receptors, Nerve Growth Factor / analysis
  • Receptors, Tumor Necrosis Factor / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / drug effects*

Substances

  • Antigens, CD
  • CD4 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Culture Media, Conditioned
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoid-Induced TNFR-Related Protein
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • TNFRSF18 protein, human