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 in:	The 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
Language:	English
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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.167.2.1125