An adjuvant, fungal immunomodulatory protein (FIP)-fve, potentiates the immune response by engaging the co-stimulatory molecules, CD27 and CD134 (OX-40)
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1
National University of Singapore, Paediatrics, Singapore
Fungal immunomodulatory protein (FIP)-fve has been shown to be an immunomodulator in tumor immunology and allergy. However, the molecular mechanism by which FIP-fve modulates the immune response to exert its adjuvant effect is yet to be elucidated. Our in vitro results demonstrated that FIP-fve required the interaction between mouse T cells and bone marrow-derived dendritic cells (BM-DCs) to induce the optimal T cell proliferation and secretion of several pro-inflammatory cytokines and chemokines, such as IFN-γ, MIG, MIP-1α, MIP-1β, and IP-10. In addition, we found that FIP-fve could directly activate T cells in a dose- and time- dependent manner, shown by the up-regulation of CD69, CD25, CD134 (OX-40), CD137 (4-1BB) on both gated CD4+T and CD8+T cells as well as CD27, CD28 on gated CD8+T cells mostly. Interestingly, blocking of the interaction between CD134 (OX-40), CD27 and their corresponding ligands significantly reduced the FIP-fve-induced T cell proliferation and cytokine/chemokine secretion. Furthermore, when FIP-fve was injected into the mouse footpad, we observed that the absolute cell number of CD4+T cells, CD8+T cells, and B cells were increased tremendously in the draining lymph node. However, our in vivo bromodeoxyuridine (BrdU)-incorporation assay suggested that the proliferating cells upon FIP-fve injection were mostly CD8+T cells and CD4+ T cells. To confirm the T cell activation in draining lymph node, FIP-fve was also shown to up-regulate the expression of CD69 and the co-stimulatory molecules, CD27 and CD28, on the gated T cells. Thus, FIP-fve may function as an adjuvant via activation and modulation of immune system.
Keywords:
adjuvants,
FIP-fve,
CD8+ T cell,
CD4+ T cells,
CD27,
CD134 (OX-40),
Fungal immunomodulatory protein
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Ong
H,
I-Chun
K and
Chiung-Hui
H
(2013). An adjuvant, fungal immunomodulatory protein (FIP)-fve, potentiates the immune response by engaging the co-stimulatory molecules, CD27 and CD134 (OX-40).
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00110
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Received:
11 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Kuo I-Chun, National University of Singapore, Paediatrics, Singapore, 117597, Singapore, paekic@nus.edu.sg
Dr. Huang Chiung-Hui, National University of Singapore, Paediatrics, Singapore, 117597, Singapore, paehch@nus.edu.sg