Abstract:
:Based on observations that DBA/2 mice develop a highly specific response towards an HLA-Cw3-derived epitope, consisting entirely of CD8+CD62L-Vbeta10+ cells, we have established an in vivo mouse model for screening a variety of immunization approaches. Responder cells were readily detectable in small samples of the peripheral blood using three-color FACS analysis. This permitted multiple, sequential determination of CD8+ T-cell responses in living animals at a very high degree of precision. In vivo electroporation delivery of expression construct plasmids, outclassed the other approaches tested. Dominant, specific responses were induced already upon a single administration. Both the peak and the longevity of the response resembled those that are generated by the most active viral infections. The induced CTLs rejected epitope-bearing tumor cells in vivo and released interferon-gamma upon stimulation with the correct MHC::peptide combination in vitro. The potent in vivo response was not influenced by known modulators of the innate immune system, such as CpG DNA and LPS content. In vivo electroporation thus deserves consideration in the future in antitumor and antiviral immunization approaches, where CD8+ T cells play a predominant role.
journal_name
Gene Therjournal_title
Gene therapyauthors
Paster W,Zehetner M,Kalat M,Schüller S,Schweighoffer Tdoi
10.1038/sj.gt.3301942keywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
717-24issue
9eissn
0969-7128issn
1476-5462pii
3301942journal_volume
10pub_type
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