Document 0110 DOCN M9550110 TI Superantigen-induced human CD4+ helper/killer T cell phenomenon. Selective induction of Th1 helper/killer T cells and application to tumor immunotherapy. DT 9505 AU Kuge S; Miura Y; Nakamura Y; Mitomi T; Habu S; Nishimura T; Department of Surgery, Tokai University School of Medicine,; Isehara, Japan. SO J Immunol. 1995 Feb 15;154(4):1777-85. Unique Identifier : AIDSLINE MED/95138521 AB Human CD4+ T cells activated with staphylococcal enterotoxin A (SEA) were fractionated by Percoll discontinuous density gradient centrifugation to enrich SEA-reactive CD4+ T cells. The SEA-reactive CD4+ T cells showed significant cytotoxicity, so-called superantigen-dependent cell-mediated cytotoxicity, against SEA-coated class II-positive tumor 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 manner. 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 from 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 specifically targeted to c-erbB-2 positive human colon cancer cells using SEA-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. DE Antibodies, Monoclonal/IMMUNOLOGY Cells, Cultured Cytotoxicity, Immunologic Enterotoxins/IMMUNOLOGY Histocompatibility Antigens Class II Human Interferon Type II/BIOSYNTHESIS Interleukin-2/BIOSYNTHESIS Killer Cells/*IMMUNOLOGY *Lymphocyte Transformation Proto-Oncogene Proteins c-erbB-2/IMMUNOLOGY Superantigens/*IMMUNOLOGY Support, Non-U.S. Gov't Th1 Cells/*IMMUNOLOGY Tumor Cells, Cultured JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).