       Document 0149
 DOCN  M9630149
 TI    Anti-metastatic activity induced by the in vivo activation of purified
       protein derivative (PPD)-recognizing Th1 type CD4+ T cells.
 DT    9603
 AU    Shinomiya Y; Harada M; Kurosawa S; Okamoto T; Terao H; Matsuzaki G;
       Shirakusa T; Nomoto K; Department of Immunology, Kyushu University,
       Japan.
 SO    Immunobiology. 1995 Aug;193(5):439-55. Unique Identifier : AIDSLINE
       MED/96089570
 AB    The Th1 type Cd4+ T cell clone (MH2), which is capable of recognizing
       purified protein derivative from Mycobacterium tuberculosis (PPD), was
       examined for its anti-metastatic activity against melanoma. In using an
       in vitro proliferative assay, MH2 was able to recognize PPD-derived
       antigen in a major histocompatibility complex class II-restricted
       manner. MH2 showed neither any natural killer (NK) activity nor
       cytolytic activity against syngeneic B16 melanoma. This clone produced
       interferon-gamma, tumor necrosis factor and interleukin-2, but not
       interleukin-4, when co-cultured with PPD and irradiated syngeneic
       C57BL/6 spleen cells, suggesting that this clone could thus be assigned
       to the Th1 subset. An intraperitoneal (i.p.) co-injection of 2 x 10(6)
       MH2 and 50 micrograms PPD increased the NK activity of the peritoneal
       exudate cells (PEC) and the percentage of NK1.1+ cells in the PEC. These
       activated NK cells showed a low but significantly cytolytic activity
       against B16 melanoma. The augmented NK activity induced by the
       co-injection of MH2 and PPD was maintained by the weekly additional i.p.
       injections of PPD alone. Using a murine metastatic model, and i.p.
       co-injection of MH2 and PPD-induced anti-metastatic activity against B16
       melanoma. This anti-metastatic activity was then abrogated by the in
       vivo administration of anti-asialo GM1 serum. In addition, the NK
       activity in both peripheral blood and metastatic lungs was significantly
       augmented in the mice which were co-injected with MH2 and PPD. Taken
       together, these findings indicate that the in vivo activation of Th1
       type CD4+ T cells augmented the NK activity in vivo and thus could
       potentially be an efficient immunotherapeutic weapon against metastasis
       of melanoma. These results also imply that adoptive immunotherapy could
       induce anti-metastatic activity through cytokine production but not
       through any direct cytolytic activity.
 DE    Adjuvants, Immunologic/ADMINISTRATION & DOSAGE/*PHARMACOLOGY  Animal
       Ascitic Fluid/IMMUNOLOGY  Clone Cells/IMMUNOLOGY/TRANSPLANTATION
       Cytotoxicity Tests, Immunologic  CD4 Lymphocyte Count  Dose-Response
       Relationship, Immunologic  Female  Immunotherapy, Adoptive  Injections,
       Intraperitoneal  Interferon Type II/ADMINISTRATION & DOSAGE  Killer
       Cells, Natural/DRUG EFFECTS  Lung Neoplasms/IMMUNOLOGY/SECONDARY/THERAPY
       Lymphocyte Transformation/*DRUG EFFECTS  Lymphoma/IMMUNOLOGY/*THERAPY
       Melanoma, Experimental/IMMUNOLOGY/*SECONDARY/*THERAPY  Mice  Mice,
       Inbred BALB C  Mice, Inbred C3H  Mice, Inbred C57BL  Sarcoma, Mast-Cell
       Support, Non-U.S. Gov't  Th1 Cells/DRUG EFFECTS/*IMMUNOLOGY
       Tuberculin/ADMINISTRATION & DOSAGE/*PHARMACOLOGY  Tumor Cells, Cultured
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

