Presentation of peptides by cultured monocytes or activated T cells allows specific priming of human cytotoxic T lymphocytes in vitro.
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.
Gagliardi
M C
MC
Istituto I Clinica Medica, Università di Roma La Sapienza, Italy.
De Petrillo
G
G
Salemi
S
S
Boffa
L
L
Longobardi
M G
MG
Dellabona
P
P
Casorati
G
G
Tanigaki
N
N
Harris
R
R
Lanzavecchia
A
A
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015789:HLA-A2 Antigen; D010455:Peptides