Biomarkers of CD4+ CTL cell mediated immunity to tuberculosis (43.51)

Abstract

Abstract The immune responses mediated by interactions between T-lymphocyte subsets and mycobacteria-infected macrophages are critical for control of tuberculosis . In these studies, the bovine model was used to characterize the cytolytic and mycobactericidal CD4+ T cell response induced by BCG vaccination. Antigenic stimulation of CD4+ T-cells from BCG vaccinated cattle induced expression of perforin and IFNgamma in cells expressing a CD45RA−, CD45RO+, and CD62L+ cell surface phenotype. Antigen specific enhancement of granulysin, IFNgamma, perforin, IL-4, IL-13, and IL-21 mRNA expression was detected and not detected for IL-2, IL-6, IL-10, IL-15, TNFα, FasL, and CD40L. Following antigenic stimulation, CD4+ T cells from BCG vaccinated animals contributed to reduction of intracellular BCG in infected macrophages. These results demonstrate that vaccination with BCG induces a subpopulation of mycobacteria-specific CD4+ T cells that are characterized by the expression of a cell-surface memory phenotype, enhanced expression of mycobactericidal molecules, and anti-mycobacterial activity against intracellular M. bovis. This work was supported by the NIAID Fellowship for Training in Emerging and Re-emerging Infectious Disease and the Sealy Center for Vaccine Development, UTMB, the Texas-United Kingdom Collaborative Research Initiative, and the Institute for Animal Health by DEFRA and the BBSRC, UK.