A tumor-specific Th2 clone initiating tumor rejection via primed CD8+ cytotoxic T-lymphocyte activation in mice.
We established a CD4+ T-cell clone specific for syngeneic methylcholanthrene-induced sarcoma, S1509a raised in an A/J mouse, involved in tumor regression. The phenotype of the T-cell clone was CD3+, TCR-beta+, CD4+, CD45RB+, LFA-1+, ICAM-1+, CD44+, and VLA-4+. The CD4+ T-cell clone specifically proliferated through antigen stimulation with attenuated S1509a in the presence of syngeneic accessory cells, and this antigen-induced proliferation was inhibited with anti-CD4 and anti-I-Ek monoclonal antibodies. The CD4+ T-cell clone designated YS1093 secreted interleukin (IL) 4, IL-5, and IL-6, but not IFN-gamma, tumor necrosis factor alpha, or IL-2, thus indicating that the clone belongs to the Th2 type. YS1093 cells and their culture supernatant after antigen stimulation augmented the primed cytotoxic T lymphocyte killing activity at the effector phase. YS1093 cells having Th2-type characteristics made the homologous growing tumor regress in the tumor-bearing syngeneic mice when YS1093 cells were transferred into the tumor-bearing mice i.v. The in vivo tumor regression initiated by YS1093 cell transfer essentially required the presence of CD8+ T cells in the tumor-bearing hosts, thus suggesting that some specific Th2 cells are positively involved in tumor regression by activating primed CD8+ cytotoxic T lymphocytes against the homologous tumor in situ.
Shen
Y
Y
Department of Immunology, Kochi Medical School, Nankoku-shi, Japan.
Fujimoto
S
S
D019264:Adoptive Transfer; D000818:Animals; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines