International Immunology Advance Access published online on November 15, 2007
International Immunology, doi:10.1093/intimm/dxm123
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Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation
1 Business Unit Biosciences, TNO Quality of Life, Zernikedreef 9, 2333 CK Leiden, The Netherlands
2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
Correspondence to: Correspondence to: J. M. Kel; E-mail: j.m.kel{at}amc.uva.nl
In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA323–339). Immunization with M-OVA323–339 in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic CD4+ T cells revealed that immunization with M-OVA323–339 induced normal clonal expansion, recirculation and CD62L expression of antigen-specific T cells in vivo. However, these T cells developed only poor effector functions, reflected by minimal IFN-
production, low IgG2a levels in serum and poor peptide-specific delayed-type hypersensitivity (DTH) responses. This diminished inflammatory response was associated with decreased infiltration of T cell blasts and macrophages. Importantly, also mice with functional effector T cells did not mount a robust DTH response after a challenge with M-OVA323–339 in the ear, although their T cells responded normally to M-OVA323–339 in vitro. In conclusion, mannosylated peptide induces proliferation of T cells with impaired Th1 cell effector functions and additionally abrogates the activity of pre-existing effector T cells.
Keywords: C-type lectins, delayed-type hypersensitivity, immune modulation, Th1 immunity
Transmitting editor: A. Cooke
Received 6 March 2007, accepted 19 October 2007.