Requirement of CD4 T cells for skin graft rejection against thymus leukemia (TL) antigen and multiple epitopes on the TL molecule recognized by CD4 T cells.
By selective depletion of CD4 and CD8 T cells in vivo using the respective mAbs, we demonstrate that CD4 T cells are necessary for skin graft rejection against thymus leukemia (TL) Ag. The skin expressing T3b-TL Ag from transgenic C3H Tg.Con.3-1 mice given chimeric H-2Kb/T3b-TL gene was rejected when grafted onto C3H/He recipient mice. Depletion of CD4, but not of CD8, T cells blocked rejection. CD8 CTL were generated in MEM (control)-treated C3H/He recipient mice, while Thy-1+ CD4- CD8- CTL were generated in CD8-depleted recipient mice after rejection. However, no CTL were generated in CD4-depleted or both CD4- and CD8-depleted recipient mice. Thus, the generation of both CD8 and Thy-1+ CD4- CD8- CTL was dependent on CD4 T cells. Ab blocking indicated that both CD8 and Thy-1+ CD4- CD8- CTL were TCR alphabeta and recognized TL Ag. We furthermore demonstrated that CD4 T cells in spleen cells from C3H/He mice that had rejected C3H Tg.Con.3-1 skin showed a weak, but significant, proliferative response to in vitro stimulation with mitomycin C-treated C3H Tg.Con.3-1 spleen cells. Analysis of the reactivity of bulk CD4 T cell lines to 73 synthetic overlapping peptides encompassing the entire T3b-TL molecule showed that CD4 T cells recognized multiple epitopes on the T3b-TL molecule in an APC-dependent manner.
Tsuji
K
K
Department of Dermatology, Okayama University Medical School, Shikata-cho, Japan.
Obata
Y
Y
Takahashi
T
T
Arata
J
J
Nakayama
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D007111:Immunity, Cellular; D015458:Leukemia, T-Cell / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D016038:Skin Transplantation / Q000276:immunology*
D000951:Antigens, Neoplasm; D000939:Epitopes