CD28-mediated T cell response is upregulated by exogenous application of autologous Hsp70–peptide complex in a tumor-bearing host

Abstract

Hsp70, a highly conserved protein, has gained plenty of attention by virtue of its adjuvant capability to induce peptide-specific cytotoxic T lymphocyte responses. In this study, we have investigated the effect of autologous Hsp70-peptide complex (or simply autologous Hsp70) on the expression of CD28 on T cells and its effector functions through macrophage activation. Further, we investigated the effect of Hsp70 on the expression of CD80 and CD86 on macrophages isolated from normal and tumor-bearing host to provide costimulatory signal for T cell activation and secretion of IL-2 and IFN-γ during interaction. We found that treatment of autologous Hsp70 effectively activated TAMs to induce higher expression of CD28 on T cells through T cells-macrophage interaction. Treatment of autologous Hsp70 induces higher expression of CD80 and CD86 on TAMs, as a result, increases B7/CD28 interaction, which in turns activates T cells and induces higher production of IL-2 and IFN-γ, thereby increasing antigen-specific T cell proliferation. With our novel study, we have provided the strong insights into the role of extracellular Hsp70 on the expression of CD28 costimulatory molecule on T cells, which helps in the activation and generation of antigen-specific T cell effector functions in a tumor-bearing host to curb malignancy.

Developing a Non-Immunogenic and Biocompatible Polymeric Self-Assembly By Using RAFT Methodology for Therapeutics Application

“…Further, 100 μl DMSO was added to each well to dissolve the formazan crystals. The absorptions were read at 540 nm in ELISA reader and results were recorded as percentage absorbance relative to untreated control cells (Kumar et al, 2016). The viability of cells was calculated with the help of following formula:…”