Recruitment and activation of tumor-specific immune t cells in situ: Functional studies using a sponge matrix model

✍ Scribed by Uwe Zangemeister; Kerstin Thiede; Volker Schirrmacher

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: French
• Weight: 766 KB
• Volume: 43
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910430225

✦ Synopsis

The activation of tumor-specific precursor cytotoxic T lymphocytes (CTLP) into cytotoxic T cells (CTL) was demonstrated in situ using the well-defined, highly metastatic ESb tumor as murine model system. Ten days after optimal immunization of syngeneic mice with a sublethal dose of live ESb tumor cells in the pinna. tumor-sensitized non-cytotoxic CTLP were recovered from the spleen and lymph nodes. These cells mature into tumor-specific CTL upon restimulation in vitro. Using a confined sponge matrix compartment, in combination with a specific tumor vaccine (autologous inactivated tumor cells), we induced a CD8+ (Lyt 2') T-cellmediated, highly cytotoxic anti-tumor immune response in situ in immunized mice. It was not possible to activate a similar response directly in lymphoid organs such as the spleen. The cytotoxic CD8+ T cells, recovered by simple mechanical pressing of the sponge, were active against the specific tumor cells in a "Cr-release assay in vitro and also in a Winn neutralization assay in vivo. CTL activity was increased and remained in the non-adherent fraction when the cell mixture, squeezed out of the sponges, was passed over nylon wool. In a cell recruitment assay, the delayed-type hypersensitivity (DTH) potential of the activated sponge-infiltrating T cells was demonstrated by their capacity to recruit circulating host lymphocytes to sites of tumor-cell location in situ.