Document 0903
 DOCN  M9650903
 TI    Presentation of peptides by cultured monocytes or activated T cells
       allows specific priming of human cytotoxic T lymphocytes in vitro.
 DT    9605
 AU    Gagliardi MC; De Petrillo G; Salemi S; Boffa L; Longobardi MG; Dellabona
       P; Casorati G; Tanigaki N; Harris R; Lanzavecchia A; et al; Istituto I
       Clinica Medica, Universita di Roma La Sapienza,; Italy.
 SO    Int Immunol. 1995 Nov;7(11):1741-52. Unique Identifier : AIDSLINE
       MED/96162432
 AB    The conditions favouring effective specific cytotoxic T lymphocyte (CTL)
       priming have been exploited to set up a simple and reproducible method
       to induce a primary CTL response in vitro. We report that cultured
       monocytes, as well as activated T cells, pulsed with exogenous HLA-A2
       binding immunogenic peptides, can induce primary peptide-specific CTL
       responses in vitro in a Th-independent manner. Primary viral
       peptide-induced CTL were HLA-A2 restricted, and recognized both
       peptide-pulsed target cells and targets infected with recombinant
       vaccinia virus expressing viral endogenous antigens. In addition, both
       cultured monocytes and activated T cells primed peptide-specific CD8+ T
       cells depleted from the CD45RO+ memory cell fraction. The efficiency of
       CTL priming by monocytes was dependent upon the strong up-regulation of
       class I, adhesion and co-stimulatory molecules occurring spontaneously
       upon in vitro culture. The inability of unseparated peripheral blood
       mononuclear cells to mount a peptide-specific CTL response could be
       reverted by direct co-stimulation of responding CD8+ T cells by soluble
       B7.1 or a stimulatory anti-CD28 antibody, that allowed a specific
       response to take place. Although co-stimulation via the B7-CD28
       interaction appeared sufficient to trigger CTL responses, it was not
       essential for CTL priming, since neither anti-B7.1 mAb nor soluble
       CTLA-4 inhibited induction of primary CTL response. This new method for
       induction of specific CD8+ T cell response in vitro may be exploited in
       adoptive immunotherapy in cancer or in HIV-infected patients.
 DE    Amino Acid Sequence  *Antigen Presentation  Antigen-Presenting
       Cells/IMMUNOLOGY  Base Sequence  Cells, Cultured  Cytotoxicity Tests,
       Immunologic  Human  HLA-A2 Antigen/IMMUNOLOGY/METABOLISM  *Lymphocyte
       Transformation  Molecular Sequence Data  Monocytes/*IMMUNOLOGY
       Peptides/*IMMUNOLOGY  Protein Binding  Support, Non-U.S. Gov't
       T-Lymphocytes/*IMMUNOLOGY  T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  JOURNAL
       ARTICLE

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