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

Abstract

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.

Functional T lymphocytes infiltrate implanted polyvinyl alcohol foams during surgical wound closure therapy

“…It would be of interest to identify, first, the different cytokines produced in the wound fluid of PVA foam‐treated patients, compared with patients without foams, and secondly, to determine which cytokines are produced in vitro by the foam T cells after bacterial stimulation. Finally, different animal models have shown that T cell infiltration inside the sponge matrices can be manipulated by prior injection of antigens and/or various cytokines [16,27–30]. Thus, PVA foams could be redesigned to improve T‐cell infiltration and T‐cell activation, for example by coating the foams with co‐stimulatory substances or by soaking them in T cell‐attracting chemokines before implantation.…”

In situ activation of syngeneic tumour-specific cytotoxic T lymphocytes: Intra-pinna immunization followed by restimulation in the peritoneal cavity

“…These cells appear to be of importance for protective immunity because of the following: (a) in our early studies we could show that the specificity of in vitro generated CTL was similar to that of protective immunity in vivo [8]; (b) some in vitro generated CTL clones could transfer protective immunity in a Winn-type assay (unpublished observations); (c) in sponge-matrix studies we demonstrated that in situ activated cytolytic CD8 + T cells from the sponges were able to transfer systemic protective immunity against ESb tumour cells [36]. In this report we show that a similar tumour-specific cytolytic T cell response can be activated not only in an artificial sponge but also in a physiological compartment such as the peritoneal cavity.…”

On the kinetics and optimal specificity of cytotoxic reactions mediated by T-lymphocyte clones

“…These CTL proliferate and infiltrate the tumour burdenl This implies an increase of the effector T cell concentration at the tumour site (see e.g. Zangemeister-Wittke et al, 1989). The immune response is also accompanied by an increase of the T cell specificity (Moscovitch et al, 1986).…”