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Different kinetic patterns of cytokine gene expression in vivo in orally tolerant mice
Author(s) -
FishmanLobell Jacqueline,
Friedman Aharon,
Weiner Howard L.
Publication year - 1994
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830241122
Subject(s) - biology , antigen , in vivo , cytokine , immune tolerance , immunology , oral administration , gene expression , immune system , peripheral tolerance , gene , pharmacology , biochemistry , genetics
Abstract A biologically relevant mechanism of generating peripheral tolerance in T cells that have escaped thymic deletion is by the oral administration of soluble antigens. Oral tolerance occurs by two distinct mechanisms. Feeding a single high dose of antigen induces anergy of antigen‐specific TH1 cells, while multiple low doses of antigen induce regulatory Tcells that mediate suppression by producing immunosuppressive cytokines. Although cytokine production in orally tolerant animals has been well studied utilizing in vitro assay systems, semi‐quantitative characterization of cytokine production in oral tolerance in vivo has not been carried out. In this paper we have developed a system using semi‐quantitative RNA polymerase chain reaction to characterize cytokine gene expression in vivo in mice orally tolerized by feeding either a single high dose or multiple low dosages of antigen. We find that measurable differences in interleukin‐4 (IL‐4) and interferon‐γ (IFN‐γ) gene expression occurred between the tolerized and non‐tolerized groups. Qualitatively, IL‐4 mRNA was increased in both orally tolerized groups. However, significant differences in IL‐4 gene expression between the two groups in both magnitude and kinetics were found. A large but short‐lived increase in IL‐4 was produced in mice fed a single high dose, while a relatively more moderate, longer‐lived increase was produced in mice fed multiple low doses. The increase in IL‐4 gene expression was specific only to the draining lymph node following antigen administration. Expression of IFN‐γ was decreased in both orally tolerant groups. These results indicate that tolerance in TH1 cells is induced by both of these feeding regimens while TH2 responses are intact and amplified upon reexposure to antigen.