title: 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.
authors.affiliation: Centre of Advanced Study, Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, U.P., 221 005, India. sanjayku15@yahoo.co.in.
authors.forename: Sanjay
authors.identifier: http://orcid.org/0000-0002-9820-4081
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Centre of Advanced Study, Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, U.P., 221 005, India.
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Gautam
authors.affiliation: Centre of Advanced Study, Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, U.P., 221 005, India.
authors.forename: Munendra Singh
authors.initials: MS
authors.lastname: Tomar
authors.affiliation: Centre of Advanced Study, Department of Zoology, Faculty of Science, Banaras Hindu University, Varanasi, U.P., 221 005, India.
authors.forename: Arbind
authors.initials: A
authors.lastname: Acharya
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D018106:CD28 Antigens; D018840:HSP70 Heat-Shock Proteins; D007376:Interleukin-2; D010446:Peptide Fragments; D007371:Interferon-gamma
keywords: Autologous Hsp70–peptide complex; CD28; CD80/86; Cytokines; T cells; Tumor-associated macrophages