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Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation

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Author: Kel, J.M. · Geus, E.D. de · Stipdonk, M.J. van · Drijfhout, J.W. · Koning, F. · Nagelkerken, L.
Type:article
Date:2008
Institution: TNO Kwaliteit van Leven
Source:International Immunology, 1, 20, 117-127
Identifier: 240594
doi: doi:10.1093/intimm/dxm123
Keywords: C-type lectins · Delayed-type hypersensitivity · Immune modulation · Th1 immunity · CD4 antigen · gamma interferon · immunoglobulin G2a · L selectin · ovalbumin · T lymphocyte receptor · animal cell · animal experiment · animal tissue · antigen expression · antigen presentation · antigen specificity · antiinflammatory activity · article · CD4+ T lymphocyte · cell fate · cellular immunity · clonal variation · controlled study · cytokine production · delayed hypersensitivity · effector cell · female · immunization · immunoglobulin blood level · in vitro study · in vivo study · lymph node · lymphoblast · lymphocyte proliferation · lymphocytic infiltration · macrophage · molecular recognition · mouse · nonhuman · priority journal · spleen cell · T lymphocyte · Th1 cell · Amino Acid Sequence · Animals · Antigen Presentation · Female · Hypersensitivity, Delayed · Immunization · Lymphocyte Activation · Mannose · Mice · Mice, Inbred C57BL · Mice, Transgenic · Molecular Sequence Data · Ovalbumin · Peptides · Receptors, Antigen, T-Cell · Th1 Cells

Abstract

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-γ 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. © The Japanese Society for Immunology. 2007. All rights reserved.