Recruitment and activation of tumor-specific immune T cells in situ: functional studies using a sponge matrix model.
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-cell-mediated, 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 51Cr-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.
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg.
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Zangemeister
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Thiede
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Schirrmacher
D000818:Animals; D002465:Cell Movement; D005260:Female; D007111:Immunity, Cellular; D007940:Leukemia L5178 / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology*; D008213:Lymphocyte Activation; D008722:Methods; D051379:Mice; D008811:Mice, Inbred DBA; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*; D013997:Time Factors