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International Immunology Advance Access published online on November 21, 2006
International Immunology, doi:10.1093/intimm/dxl121
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received January 3, 2006
Accepted October 23, 2006

Article

Increased antigen presentation and Th1 polarization in genetically histamine-free mice

Ivett Jelinek 1, Valéria László 1 *, Edit Buzás 1, Éva Pállinger 2, Balázs Hangya 1, Zsuzsanna Horváth 1, and András Falus 3

1 Department of Genetics, Cell and Immunobiology, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary
2 Immunogenomics Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary
3 Department of Genetics, Cell and Immunobiology, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary; Immunogenomics Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary

* To whom correspondence should be addressed.
Valéria László, E-mail: laszval{at}dgci.sote.hu


  Abstract

Histamine is a well-known inflammatory mediator exerting various immunomodulatory effects and affecting the development of antigen-specific immune responses. Dendritic cells (DCs) are the most potent antigen-presenting cells specialized for capture, uptake, transport, processing and presentation of antigens to T cells. Using a genetically histamine-free [histidine decarboxylase knockout (HDC-/-)] mouse model, we examined the effects of histamine on DC-mediated antigen presentation. Applying an in vitro antigen presentation assay, we found that spleen DCs, derived from HDC-/- mice, display a higher efficiency in antigen presentation compared with wild-type cells. Flow cytometric characterization of DCs disclosed that this difference was not due to an altered distribution of DCs between or within the major functional sub-populations (assessed by CD11b and CD4 as myeloid and CD8{alpha} and DEC205 as lymphoid DC markers) or major changes in the co-stimulatory molecule profile (CD40, CD80, CD86). However, real-time PCR analysis of in vivo CFA-induced IL-12p35, IFN{gamma}, IL-10 and IL-4 expression showed that DCs matured in a histamine-free environment exhibit significantly elevated levels of IL-12p35 and IFN{gamma} mRNA. In vitro investigations confirmed that isolated DCs, developed in the absence of histamine, exhibit indeed a predominantly Th1-polarized cytokine pattern, as they show elevated levels of IFN{gamma} mRNA upon LPS stimulation. Similar difference was found at the protein level by ELISA, as well. Our study demonstrates that histamine interferes with antigen presentation and alters the cytokine profile of DCs.

Keywords: antigen presentation; cytokine; dendritic cell; histamine; Th1 response.
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