Evaluation of bovine dendritic cells in the induction of cytotoxic T lymphocyte responses to Theileria Parva
Abstract
Recent demonstration of an ability of human and murine dendritic cells (DC) to
acquire exogenous antigens, present them as peptide complexes with MHC class I
molecules and induce antigen specific CD8+ cytotoxic T lymphocyte (CTL)
responses, a process termed cross-presentation, has led to a reassessment of the role
that dendritic cells play in the initiation of immune responses against tumours and
microbial pathogens whose elimination is mediated by CTL. Protective immunity
against a bovine parasite, Theileria parva, has been shown to be mediated by major
histocompatibility complex (MHC) class I restricted CD8+ CTL, which kill
lymphocytes infected with the schizont stage of the parasite. This study investigated
whether bovine dendritic cells could acquire and present exogenous T. parva
schizont antigens and induce MHC class I restricted CD8+ CTL responses. Purified
bovine monocytes were successfully differentiated into DC by culture in the presence
of Interleukin-4 (IL-4) and Granulocyte Macrophage-Colony Stimulating Factor
(GM-CSF), and matured by the addition of Lipopolysaccharide (LPS) or Tumour
Necrosis Factor-alpha (TNF-a). Compared to Monocytes, DC were superior in their
ability to stimulate allogeneic or recombinant T. parva antigen specific proliferative
T cell responses. In the_absence of defined T. parva-antigens known to be recognised
by CTL, the ability of DC to recall schizont specific CTL from immune cattle was
assessed by use of intact schizonts purified from infected cells. DC presented
schizont antigens inducing Peripheral Blood Mononuclear Cells (PBMC) to
proliferate and produce Interferon gamma (IFN-y). Significantly, schizont pulsed DC
also stimulated an increase in the proportion of CD8+ T cells expressing perforin
suggesting that schizont antigens were cross-presented and CTL induced. Whether
these perforin expressing CD8+ T cells are schizont specific CTL remains to be
determined. This study has provided data to support the further development of DC
targeted protein vaccines against T. parva and other pathogens where protective
immunity requires the induction of MHC class I restricted CTL
Publisher
School of Biological Sciences, University of Nairobi
Description
Master of Science in Applied Parasitology (Immunoparasitology)