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

• Published in: Immunologic research Vol. 64; no. 1; pp. 313 - 323
• Main Authors: Kumar, Sanjay, Gautam, Pramod Kumar, Tomar, Munendra Singh, Acharya, Arbind
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2016; Springer Nature B.V
• Subjects: Allergology; Animals; Autoantigens - immunology; Autoantigens - metabolism; Biomedical and Life Sciences; Biomedicine; CD28 Antigens - metabolism; Cell Communication; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cellular biology; Cytokines; HSP70 Heat-Shock Proteins - immunology; HSP70 Heat-Shock Proteins - metabolism; Humans; Immunology; Interferon-gamma - metabolism; Interleukin-2 - metabolism; Internal Medicine; Lymphoma - immunology; Macrophage Activation; Macrophages - immunology; Medicine/Public Health; Mice; Mice, Inbred BALB C; Original Article; Peptide Fragments - immunology; Peptide Fragments - metabolism; Peptides; Proteins; T-Lymphocytes - immunology; Tumors; CD28; CD80/86; Cytokines; T cells; Autologous Hsp70–peptide complex; Tumor-associated macrophages
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-015-8752-z

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.