IL-4 utilizes an alternative receptor to drive apoptosis of Th1 cells and skews neonatal immunity toward Th2.
Primary neonatal Th1 cells develop alongside of Th2 upon priming of the newborn but undergo apoptosis upon recall with antigen. These Th1 cells were isolated, and their death was correlated with elevated IL-13Ralpha1 chain expression. Strikingly, neutralization of Th2s' IL-4 reduced apoptosis, sustained recall responses, and the live Th1 cells displayed a decrease in IL-13Ralpha1 expression. Blockade of IL-13Ralpha1 or IL-4Ralpha also restores recall and secondary Th1 responses. Adult T cells primed within the neonatal environment did not upregulate IL-13Ralpha1 chain or undergo apoptosis and developed recall Th1 responses. These observations indicate that developmental expression of IL-13Ralpha1 along with IL-4Ralpha provides a receptor through which IL-4 induces death of Th1 cells and skews neonatal immunity toward Th2.
Li
Lequn
L
Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, M616 Medical Sciences Building, Columbia, MO 65212 USA.
Lee
Hyun-Hee
HH
Bell
J Jeremiah
JJ
Gregg
Randal K
RK
Ellis
Jason S
JS
Gessner
Andre
A
Zaghouani
Habib
H
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D020169:Caspases / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D053660:Receptors, Interleukin-13; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
C508183:Il13ra1 protein, mouse; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4; D020169:Caspases