       Document 0353
 DOCN  M9630353
 TI    CD8 T cell clones inhibit antitumor T cell function by secreting IL-10.
 DT    9603
 AU    Rohrer JW; Coggin JH Jr; University of South Alabama College of
       Medicine, Department of; Microbiology and Immunology, Mobile 36688, USA.
 SO    J Immunol. 1995 Dec 15;155(12):5719-27. Unique Identifier : AIDSLINE
       MED/96094467
 AB    We have reported that in irradiated, long-term surviving RFM strain of
       mice there is enhanced kinetics of tumor development upon challenge with
       RFM lymphoma cells. We reported that we cloned splenic oncofetal
       (OFA)-specific, noncytotoxic CD8+ T cells from such mice. These
       noncytotoxic CD8+ T cell clones secrete a factor upon Ag stimulation
       that inhibits the ability of OFA-specific RFM cytotoxic T (TC) cell
       clones from killing 5T RFM lymphoma cells in vitro. These supernatants
       do not inhibit the tumor cell-induced proliferation of the TC cell
       clones however. We report here that OFA-stimulated, RFM-noncytotoxic CD8
       T cell clone culture supernatants also inhibit IFN-gamma-secretion by
       stimulated CD4 and CD8 RFM anti-OFA effector T cell clones in a
       dose-dependent manner. The inhibitor in those culture supernatants acts
       in neither an Ag-specific nor MHC-restricted manner. We find that the
       culture supernatants of OFA-stimulated, noncytotoxic CD8 T cell clones
       contain IL-10, while those from OFA-stimulated, RFM OFA-specific TC cell
       clones do not. We show that monoclonal anti-IL-10 Ab specifically blocks
       the inhibition of cytotoxic activity and IFN-gamma secretion by
       OFA-specific CD8 and CD4 effector T cell clones in a dose-dependent
       manner in vitro. Incorporation of anti-IL-10 Ab into the cytotoxicity
       assays of the OFA-specific, noncytotoxic CD8+ T cell clones against 5T
       tumor cells restores their cytotoxic activity. This may suggest that one
       way of inducing anergic T cells is by induction of IL-10 secretion.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY  Antigens, Neoplasm/IMMUNOLOGY
       Clone Cells  Culture Media  CD4-Positive T-Lymphocytes/METABOLISM
       CD8-Positive T-Lymphocytes/IMMUNOLOGY/*METABOLISM  Female  H-2
       Antigens/GENETICS  Immunologic Surveillance/DRUG EFFECTS  Interferon
       Type II/BIOSYNTHESIS
       Interleukin-10/*BIOSYNTHESIS/IMMUNOLOGY/*PHARMACOLOGY  Lymphoma  Male
       Mice  Mice, Inbred Strains  Support, U.S. Gov't, P.H.S.  Tumor Cells,
       Cultured  JOURNAL ARTICLE

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

