Possible involvement of autoreactive CD4 T cells in generation of cytotoxic T lymphocytes on in vitro stimulation with H-2 class I-binding tumor antigen peptide.
We demonstrated that RL male 1-specific cytotoxic T lymphocytes (CTL) were generated in spleen cells from the tumor-rejected CB6F1 mice on in vitro stimulation with Ld-binding pRL1a peptide. We showed that CD4 T cells and antigen-presenting cells were necessary for CTL generation. Furthermore, CTL generation was inhibited by the addition of anti-I-Ad mAb, but not anti-I-Ek/d mAb, to the culture. However, no binding of the pRL1a peptide to the I-Ad molecule could be demonstrated. No inhibition by the pRL1a peptide of I-Ad-restricted IL-2 production by ovalbumin (OVA)-specific CD4 T cell hybridoma DO-11.10 was observed on stimulation with the specific OVA peptide. Moreover, no specific proliferative response or IL-2 production was observed with CD4 T cells in spleen cells from the tumor-rejected mice on stimulation with a range of mitomycin C-treated RL male 1 cells, or with RL male 1 lysate or the pRL1a peptide. Rather, the activation of autoreactive CD4 T cells and the IL-2 production from them were observed. CD4 T cells from CB6F1 mice that had rejected other tumors such as EL4 or MOPC-70A also helped the generation of pRL1a-specific CTL. These findings suggested the involvement of autoreactive CD4 T cells in CTL generation against the pRL1a peptide.
Honda
S
S
Department of Parasitology and Immunology, Okayama University Medical School, Japan.
Wada
H
H
Uenaka
A
A
Nakayama
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000096:biosynthesis; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008211:Lymphocyte Cooperation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D007376:Interleukin-2; D010455:Peptides; D010047:Ovalbumin; D004247:DNA