Document 0404
 DOCN  M9550404
 TI    CD4 T cells inhibit in vivo the CD8-mediated immune response against
       murine colon carcinoma cells transduced with interleukin-12 genes.
 DT    9505
 AU    Martinotti A; Stoppacciaro A; Vagliani M; Melani C; Spreafico F; Wysocka
       M; Parmiani G; Trinchieri G; Colombo MP; Division of Experimental
       Oncology D, Istituto Nationale per lo; Studio e la Cura dei Tumori,
       Milano, Italy.
 SO    Eur J Immunol. 1995 Jan;25(1):137-46. Unique Identifier : AIDSLINE
       MED/95145517
 AB    Retroviral-mediated cytokine gene transfer into tumor cells is a highly
       effective way of inducing tumor inhibition and immunity. We analyzed the
       tumorigenicity of C-26 murine colon carcinoma cells transduced with
       genes encoding the two subunits of murine interleukin-12 (IL-12) in a
       polycistronic retroviral vector and selected for resistance to G418 and
       for IL-12 production (30-80 pg/ml). BALB/c mice injected s.c., i.v. and
       intrasplenically with C-26/IL-12 cells from three different
       IL-12-producing clones showed delayed tumor onset as compared with mice
       injected with control NeoR-transduced or parental tumor cells. Although
       C-26/IL-12 tumor-bearing mice eventually died of lung metastasis, their
       survival time was twice as long as that of mice injected with control
       cells. In experiments with mice selectively depleted of natural killer
       (NK) cells before tumor cell injection, the time of tumor onset and
       survival of mice injected with C-26/IL-12 s.c. and i.v., respectively,
       was reduced. CD8+ T cell depletion had no effect on latency or survival,
       whereas removal of CD4+ T cells led to C-26/IL-12 tumor regression in
       about 40% of mice. Histological and immunocytochemical characterization
       of leukocytes infiltrating C-26/IL-12 tumors showed only slight
       infiltration with few T cells in non-depleted mice but abundant
       infiltration by CD8+ T cells and asialo-GM1+ NK cells in tumors of mice
       depleted of CD4+ T cells. The lack of CD8+ T cell infiltration is not
       due to a CD4-mediated suppression of their activation because irradiated
       C-26/IL-12 cells primed for the induction of a strong cytotoxic T
       lymphocyte response against C-26 parental cells and induced CD8+
       effector cells that protected against C-26/IL-12 in a Winn assay.
       Rather, the results suggest that, although C-26/IL-12 cells injected in
       vivo stimulate both NK and CD8+ T cells, tumor infiltration by the
       latter is inhibited by CD4+ T cells.
 DE    Animal  Base Sequence  Colonic Neoplasms/IMMUNOLOGY  Cytotoxicity Tests,
       Immunologic  CD4-Positive T-Lymphocytes/*IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  DNA, Neoplasm/GENETICS  Gene Therapy
       Immunoenzyme Techniques  Immunotherapy, Adoptive/METHODS
       Interleukin-12/BIOSYNTHESIS/GENETICS/*IMMUNOLOGY  Lymphocyte Culture
       Test, Mixed  Mice  Mice, Inbred BALB C  Molecular Sequence Data
       Neoplasm Transplantation/IMMUNOLOGY  Neoplasms,
       Experimental/*IMMUNOLOGY/PATHOLOGY/THERAPY  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  Transfection/*GENETICS  Tumor Cells,
       Cultured  JOURNAL ARTICLE

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