University of Tasmania
Browse

File(s) not publicly available

Human Flt-3-ligand-mobilized dendritic cells require additional activation to drive effective immune responses

journal contribution
posted on 2023-05-17, 08:34 authored by Diener, KR, Moldenhauer, L, Alan Lyons, Brown, MP, Hayball, JD
OBJECTIVE: Dendritic cells (DCs) play a pivotal role in the induction of immunity in response to pathogenic challenge or vaccination. As such, the fms-like tyrosine kinase 3-ligand (Flt-3L) has been used to increase DC populations in vivo, with contrasting outcomes, which include an increase in immunity, tolerance induction, or expansion of regulatory cells. This study examines the adjuvant role that human Flt-3L (hFL) administration has in generating immune responses upon immunization with a poorly immunogenic and soluble protein antigen. MATERIALS AND METHODS: Mice were immunized with the nominal antigen, ovalbumin, alone or with antigen emulsified in complete Freund's adjuvant (CFA), with or without prior hFL-mediated expansion of DC subsets. The maturation of DC subsets and activation status of antigen-specific T cells were analyzed by flow cytometry, with effector function assessed in cytolytic T-lymphocyte assays. RESULTS: hFL treatment expanded both conventional DC and plasmacytoid DC in vivo, resulting in increased antigen presentation by both direct and cross-presentation pathways. However, it was only in the context of CFA that antigen immunization could mature DCs and subsequently fully activate antigen-specific T cells with enhanced cytolytic activity. CONCLUSIONS: Our studies reveal that hFL essentially acts as a coadjuvant, as hFL augments the size of an immune response but requires further adjuvant activation to alter the quality of the response

History

Publication title

Experimental Hematology

Volume

36

Pagination

51-60

ISSN

0301-472X

Department/School

Tasmanian School of Medicine

Publisher

Elsevier Science Inc

Place of publication

360 Park Ave South, New York, USA, Ny, 10010-1710

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC