SUPERANTIGEN-INDUCED HUMAN CD4(-CELL PHENOMENON - SELECTIVE INDUCTIONOF TH1 HELPER KILLER T-CELLS AND APPLICATION TO TUMOR-IMMUNOTHERAPY()HELPER KILLER T)

Human CD4(+) T cells activated with staphyloccocal enterotoxin A (SEA) were fractionated by Percoll discontinuous density gradient centrifug ation to enrich SEA-reactive CD4(+) T cells. The SEA-reactive CD4(+) T cells showed significant cytotoxicity, so-called superantigen-depende nt cell-mediated cytotoxicity, against SEA-coated class Ii-positive tu mor cells. During lysis of SEA-coated tumor cells, SEA-reactive CD4(+) T cells produced high levels of IL-2 and IFN-gamma but not IL-4 in an Ag-specific man ner. The skewing of human CD4(+) T cells to Th1-type helper/killer T cells was also demonstrated when SEA-reactive CD4(+)V beta 5.3(+) clonal T cells were cultured with SEA, but not with PHA or OKT3 mAb. Interestingly, the generation of SEA-reactive helper/killer T cells was negatively regulated by IL-4, but up-regulated by IL-12. The SEA-reactive CD4(+) helper/killer T cells were able to generate fr om PBMC of tumor patients and could be expanded to 10(9) levels in a 7 -day culture. The SEA-reactive CD4(+) helper/killer T cells were speci fically targeted to c-erbB-2 positive human colon cancer cells using S EA-conjugated-anti-c-erbB-2 mAb. These results initially demonstrated that SEA-activated human CD4(+) T cells are a Th1 type of Th cell that has both helper and killer functions which may be useful for adoptive tumor immunotherapy in combination with SEA-conjugated antitumor mAb.