B7.1 expression on tumor cells circumvents the need of professional antigen presentation for in vitro propagation of cytotoxic T cell lines.
In vitro propagation of tumor-specific CTLs, to be used for identification of tumor antigens (Ag) and/or adoptive immunotherapy, is hampered by the need of large amounts of professional antigen-presenting cells (APC) used for periodical cycles of restimulation. We evaluated whether RMA T lymphoma cells, stably transfected with the cDNA encoding for the B7.1 costimulatory molecule, provided the activation signals to CD8+ T lymphocytes in the absence of professional APC and CD4+ helper cells. We demonstrate here that long-term CD8+ cell lines can be efficiently propagated in vitro by repeated cycles of stimulation with tumor cells stably expressing B7.1. Professional APC and CD4+ helper cells are not required as far as interleukin 2 is exogenously provided. Furthermore, CD8+ blasts needed both signal 1 (Ag in the contest of the MHC molecule) and signal 2 (interaction of costimulatory molecules) for restimulation. T cell blasts in the presence of signal 1 or 2 only still retained their effector potential but did not undergo clonal expansion. These results are very promising for further applications of specific immunotherapies in humans.
Laboratorio I.A., Istituto Scientifico H San Raffaele, Milano, Italy.
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G
Iezzi
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Protti
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Rugarli
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Bellone
D017951:Antigen Presentation / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D018076:DNA, Complementary