title: 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.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Xiufang
authors.initials: X
authors.lastname: Weng
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liang
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Lichen
authors.initials: L
authors.lastname: Ouyang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D002478:Cells, Cultured; D018920:Coculture Techniques; D019281:Dimerization; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D059810:HLA-DR Serological Subtypes / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*
chemical_list: D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D007141:Immunoglobulin Fc Fragments; D010455:Peptides; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma