Tumor rejection effects of allorestricted tumor peptide-specific CD4(+) T cells on human cervical cancer cell xenograft in nude mice.

Abstract

Generation of tumor specific alloreactive CD4(+) T cells is important to circumvent tumor tolerance. Here, we generate allorestricted peptide-specific CD4(+) T cells by coculture of lymphocytes and autologous monocytes bearing allogeneic HLA-DR15 molecule associated with its restricted peptide. Binding of a dimeric HLA-DR15/IgG1-Fc fusion protein (the dimer) to HLA-DR15 negative (HLA-DR15-ve) monocytes made the monocytes coated with the allogeneic epitope. An increased proliferation of CD4(+) T cells and induction of Th1 cells appeared after coculturing of HLA-DR15-ve lymphocytes and the autologous monocytes loaded with the dimer. The cocultural bulks showed an increased frequency of the specific dimer-stained CD4(+) T cells and the expanded CD4(+) T cells exhibited an elevated IFN-γ production in response to specific TCR ligand. Tumor rejection effects of the allorestricted E7-specific CD4(+) T cells raised by the coculture were observed in nude mice challenged with human cervical cancer cell SiHa expressing both HLA-DR15 and E7 antigens, as the tumor avoidance and life span of the mice were improved after adoptive transfer of the CD4(+) T cells. This study may help to develop strategies to separate graft-versus-leukemia or graft-versus-tumor reaction from graft-versus-host disease, and add to the pool of human high-avidity TCRs specific for tumor or virus antigens.

• Authors: Yinhong Song, Wei Sun, Xiufang Weng, Zhihui Liang, Qian Yu, Zhigang Wang, Lichen Ouyang, Jun Chen, Xiaolin Wu, Guanxin Shen, Xiongwen Wu
• Journal: Cell transplantation (Cell Transplant) Vol. 21 Issue 7 Pg. 1503-14 ( 2012) ISSN: 1555-3892 [Electronic] United States
• PMID: 22525838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DR Serological Subtypes
• HLA-DR15 antigen
• Immunoglobulin Fc Fragments
• Peptides
• Recombinant Fusion Proteins
• Interferon-gamma

Topics

• Animals
• CD4-Positive T-Lymphocytes (cytology, metabolism, transplantation)
• Cells, Cultured
• Coculture Techniques
• Dimerization
• Female
• Graft vs Host Disease (immunology, pathology)
• HLA-DR Serological Subtypes (genetics, metabolism)
• HeLa Cells
• Humans
• Immunoglobulin Fc Fragments (genetics, metabolism)
• Interferon-gamma (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Monocytes (cytology, immunology, metabolism)
• Peptides (genetics, metabolism)
• Recombinant Fusion Proteins (biosynthesis, genetics, immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Th1 Cells (cytology, immunology)
• Transplantation, Heterologous
• Uterine Cervical Neoplasms (immunology, metabolism, therapy)