TNF-Mediated Toxicity After Massive Induction of Specific CD8+ T Cells Following Immunization of Mice with a Tumor-Specific Peptide

摘要: We immunized mice with antigenic peptide P815E, which is presented by H-2K(d) and recognized tumor-specific CTL raised against P815 tumor cells. This encoded the ubiquitously expressed gene MsrA carries a mutated residue conferring specificity. Unexpectedly, we observed severe toxicity occurring in early hours after third injection, resulting death of most within 24 h. The toxic syndrome was reminiscent TNF-induced shock, sera ill contained high levels TNF. Toxicity prevented injection neutralizing anti-TNF Abs, confirming involvement Depletion CD8(+) T cells could also prevent toxicity, ex vivo experiments confirmed that lymphocytes were major cellular source TNF mice. Tetramer analysis indicated massive expansion P815E-specific cells, up to >60% circulating CD8+ lymphocytes. A similar specific following immunization another peptide, P1A injected form covalently linked an immunostimulatory derived from IL-1. conclude caused lymphocytes, are extensively amplified QS21-based adjuvant produce upon further stimulation peptide. Our results suggest immunotherapy trials involving new peptides should be pursued caution include careful monitoring cell response.