Failure to Induce Neonatal Tolerance in Mice That Lack Both IL-4 and IL-13 but Not in Those That Lack IL-4 Alone

Current evidence suggests that neonatal tolerance to a foreign Ag is the consequence of IL-4-mediated Th2 immunity rather than the thymic deletion of Ag-specific T cells. Here, we addressed the role of IL-4 in neonatal tolerance by testing whether tolerance to a minor histocompatibility Ag can be in...

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Published inThe Journal of immunology (1950) Vol. 167; no. 2; pp. 1125 - 1128
Main Authors Inoue, Yoshihiko, Konieczny, Bogumila T, Wagener, Maylene E, McKenzie, Andrew N. J, Lakkis, Fadi G
Format Journal Article
LanguageEnglish
Published United States Am Assoc Immnol 15.07.2001
Subjects
Animals
Animals, Newborn - genetics
Animals, Newborn - immunology
Female
H-Y Antigen - administration & dosage
H-Y Antigen - immunology
Immune Tolerance - genetics
Injections, Intraperitoneal
Interferon-gamma - antagonists & inhibitors
Interferon-gamma - biosynthesis
Interleukin-13 - deficiency
Interleukin-13 - genetics
Interleukin-4 - deficiency
Interleukin-4 - genetics
Interleukin-4 - physiology
Lymphocyte Transfusion
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Skin Transplantation - immunology
Spleen - cytology
Spleen - transplantation
Th2 Cells - immunology
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Summary:Current evidence suggests that neonatal tolerance to a foreign Ag is the consequence of IL-4-mediated Th2 immunity rather than the thymic deletion of Ag-specific T cells. Here, we addressed the role of IL-4 in neonatal tolerance by testing whether tolerance to a minor histocompatibility Ag can be induced in newborn mice that lack IL-4 (IL-4(-/-)). We found that IL-4 does not play a dominant role in the induction of neonatal tolerance as newborn female IL-4(-/-) mice could be readily tolerized to the H-Y male Ag. In contrast, mice that lack both IL-4 and IL-13 (IL-4(-/-)/IL-13(-/-)) were resistant to the induction of neonatal tolerance, and their splenocytes produced exaggerated amounts of IFN-gamma on rechallenge with the same Ag encountered during the neonatal period. These findings argue against the view that IL-4 alone is critical for the induction of neonatal tolerance and suggest that the combined actions of both IL-4 and IL-13 are essential for this process.
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ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.167.2.1125