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M9550110.TXT
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1995-03-04
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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).