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Gamma-delta T cell activators to stimulate immune responses in early life
Summary

Gamma-delta T cells are innate lymphocytes able to react rapidly upon infection. Besides their direct effector function, cross-talk between adult gamma-delta T cells and dendritic cells influences adaptive immune responses. Dendritic cells from human newborns have a lower capacity than their adult counterparts to activate T helper lymphocytes. In this project, we will investigate the cross-talk between gamma-delta T cells and dendritic cells from cord blood in vitro. The reciprocal activation of dendritic cells and gamma-delta T cells in response to phosphoantigens, Mycobacterium bovis Bacille Calmette-Guérin (BCG) and Toll-like receptor ligands will be compared in adults and newborns. In parallel, in vivo activation of gamma-delta T cells and its possible association with dendritic cell activation will be investigated in infants vaccinated at birth with BCG. Information gained in this project will help us to understand the role of gamma-delta T cells in neonatal immunity and will hopefully contribute to the development of new vaccination strategies using gamma-delta T cells as targets for efficient adjuvants.

Research team

Principal investigator: David VERMIJLEN (PhD), Fabienne WILLEMS (PHD)
PhD student: Emmanuelle MOENS
Post-doctoral fellow: Tanya DIMOVA

External Collaborator

M. EBERL, Cardiff University, UK
W. HANEKOM, University of Cape Town, South Africa

Key reference

Danis B, George TC, Goriely S, Dutta B, Renneson J, Gatto L, Fitzgerald-Bocarsly P, Goldman M, Willems F, De Wit D. Interferon regulatory factor 7 dependent responses are deficient in cord blood plasmacytoid dendritic cells Eur J Immunol 2008 ; 37 : 507-517.

Vermijlen D, Ellis P, Langford C, Klein A, Engel R, Willimann K, Jomaa H, Hayday AC, Eberl M. Distinct cytokine-driven responses of activated blood gamma-delta T cells: insights into unconventional T cell pleiotropy. Journal of Immunology 2007;178:4304-4314.

Aksoy E, Albarani V, Nguyen M, Laes JF, Ruelle JL, De Wit D, Willems F, Goldman M, Goriely S. IRF3-dependent responses to LPS are selectively blunted in human cord blood. Blood 2007 ; 109 : 2887-2893.

Vanden Eijnden S, Goriely S, De Wit D, Goldman M, Willems F. Preferential production of the IL-12(p40) / IL-23(p19) heterodimer by dendritic cells from human newborns. Eur J Immunol 2006 ; 36 : 21-26.

De Wit D, Olislagers V, Goriely S, Vermeulen F, Wagner H, Goldman M, Willems F. Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns. Blood 2004 ; 103 : 1030-1032.

 

Sponsors

Government of the Walloon Region
GSK Biologicals
The Fund for Scientific Research (F.R.S - FNRS) and the Télévie Programme
The Belgian Science Policy

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