title: Evaluation of CD4+/CD8+ T-cell expression and IFN-γ, perforin secretion for B-T constructs of F1 and V antigens of Yersinia pestis.
abstract: Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Understanding the immune response generated by epitopes recognized by CD4+ and CD8+ T cells is important for the development of safe and effective vaccines designed to promote protective cellular immunity. Apart from humoral response, CD4+ T cells have shown to have a major role in combating the pneumonic form of the disease. In the present study, the secretion of IFN-γ and IL-4 by splenocytes, stimulated by different constructs of B and T cell epitopes of F1 and V antigens, was measured by ELISpot assay. We also measured perforin and IFN-γ expression as a function of cell mediated immunity by flow cytometry. Three B-T constructs of F1 and seven B-T constructs of V antigens produced a high number of IFN-γ secreting cells as compared to native antigen and a low number of IL-4 secreting cells. B-T conjugates of F1 and V antigens showed significantly high (p<0.001) percentage of CD4+ IFN-γ(+) cells as compared to CD8+ IFN-γ(+) cells. Thus, the study highlights the importance of Th1 cytokine and existence of high proportion of CD4+ T cells probably contributing protection in the host. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Gupta
authors.forename: Riyasat
authors.initials: R
authors.lastname: Ali
authors.forename: Arif Azam
authors.initials: AA
authors.lastname: Khan
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology; D054353:Perforin / Q000276:immunology; D010930:Plague / Q000517:prevention & control; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D014611:Vaccination; D015010:Yersinia pestis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; C043908:LcrV protein, Yersinia; D010455:Peptides; D052899:Pore Forming Cytotoxic Proteins; C086725:caf1 protein, Yersinia pestis; D054353:Perforin; D015847:Interleukin-4; D007371:Interferon-gamma