Journal article
Attenuation of Th1 Effector Cell Responses and Susceptibility to Experimental Allergic Encephalomyelitis in Histamine H 2 Receptor Knockout Mice Is Due to Dysregulation of Cytokine Production by Antigen-Presenting Cells
The American journal of pathology, v 164(3), pp 883-892
2004
PMID: 14982842
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Histamine, a biogenic amine with both neurotransmitter and vasoactive properties, is well recognized as an immunomodulatory agent in allergic and inflammatory reactions. It also plays a regulatory role in the development of antigen-specific immune responses. CD4
+ T-cells from histamine H
1 receptor (H1R)-deficient (H1RKO) mice produce significantly less interferon-γ and more interleukin (IL)-4 in
in vitro
recall assays compared to wild-type controls. H1RKO mice are also less susceptible to acute early-phase experimental allergic encephalomyelitis indicating that H1R signaling in CD4
+ T cells plays a central role in regulating pathogenic T-cell responses. In this study, we show that mice lacking histamine H
2 receptor (H2RKO) are similar to H1RKO mice in that they develop encephalitogen-specific T-cell responses as assessed by proliferation and IL-2 production and present with less severe acute early-phase experimental allergic encephalomyelitis. However, unlike T cells from H1RKO mice, which exhibit a strong Th2 bias, T cells from H2RKO mice do not. Rather, they are uniquely characterized by a significant inhibition of Th1 effector cell responses. Given that both histamine and adjuvants such as pertussis toxin modulate antigen-presenting cell (APC) maturation and function, including T-cell-polarizing activity, we analyzed the cytokines/chemokines secreted by APCs from wild-type, H1RKO, and H2RKO mice. Significant differences in cytokine/chemokine production by APCs from unimmunized and immunized mice were delineated. APCs from H2RKO mice produce significantly less IL-12 and IL-6 and markedly greater amounts of MCP-1 compared to wild-type and H1RKO mice. Because MCP-1 is known to inhibit IL-12 production, the failure of H2RKO mice to generate encephalitogenic Th1 effector cell responses is consistent with inhibition of negative regulation of MCP-1 secretion by H2R signaling in APCs.
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Details
- Title
- Attenuation of Th1 Effector Cell Responses and Susceptibility to Experimental Allergic Encephalomyelitis in Histamine H 2 Receptor Knockout Mice Is Due to Dysregulation of Cytokine Production by Antigen-Presenting Cells
- Creators
- Cory Teuscher - Department of Medicine, University of Vermont School of Medicine, Burlington, VermontMatthew E Poynter - Department of Medicine, University of Vermont School of Medicine, Burlington, VermontHalina Offner - Department of Neurology, Oregon Health and Science University and Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OregonAlex Zamora - Department of Neurology, Oregon Health and Science University and Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OregonTakeshi Watanabe - Medical Institute of Bioregulation, Kyushu University, Fukuoka, JapanParley D Fillmore - Department of Veterinary Pathobiology, University of Illinois at Urbana–Champaign, Urbana, IllinoisJames F Zachary - Department of Veterinary Pathobiology, University of Illinois at Urbana–Champaign, Urbana, IllinoisElizabeth P Blankenhorn - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- The American journal of pathology, v 164(3), pp 883-892
- Publisher
- Elsevier
- Grant note
- RG-3129 to C.T and E.P.B., AI42376 to H.O., NS23444 to H.O., and RG-3108 to H.O. / National Multiple Sclerosis Society NS36526 to C.T. and E.P.B., AI4515 to C.T., AI41747 to C.T. / National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000189164300014
- Scopus ID
- 2-s2.0-1242271339
- Other Identifier
- 991014878124304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pathology