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 T-h-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.
PRESENTATION OF PEPTIDES BY CULTURED MONOCYTES OR ACTIVATED T-CELLS ALLOWS SPECIFIC PRIMING OF HUMAN CYTOTOXIC T-LYMPHOCYTES IN-VITRO / Maria Cristina, Gagliardi; G., De Petrillo; Simonetta, Salemi; Laura, Boffa; Maria Grazia, Longobardi; Paolo, Dellabona; Giulia, Casorati; Nabuyuki, Tanigaki; Reuben, Harris; Antonio, Lanzavecchia; Barnaba, Vincenzo. - In: INTERNATIONAL IMMUNOLOGY. - ISSN 0953-8178. - 7:11(1995), pp. 1741-1752. [10.1093/intimm/7.11.1741]
PRESENTATION OF PEPTIDES BY CULTURED MONOCYTES OR ACTIVATED T-CELLS ALLOWS SPECIFIC PRIMING OF HUMAN CYTOTOXIC T-LYMPHOCYTES IN-VITRO
BARNABA, Vincenzo
1995
Abstract
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 T-h-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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.