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 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.
Inoue
Y
Y
Renal Division, Department of Medicine, Emory University and Veterans Affairs Medical Center, 1670 Clairmont Road, Atlanta, GA 30033, USA.
Konieczny
B T
BT
Wagener
M E
ME
McKenzie
A N
AN
Lakkis
F G
FG
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics* / Q000276:immunology*; D005260:Female; D006182:H-Y Antigen / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics*; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018793:Interleukin-13 / Q000172:deficiency* / Q000235:genetics*; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology
D006182:H-Y Antigen; D018793:Interleukin-13; D015847:Interleukin-4; D007371:Interferon-gamma