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Title: AN IL-4-INDEPENDENT PATHWAY FOR CD4+ T CELL IL-4 PRODUCTION IS REVEALED IN IL-4 RECEPTOR DEFICIENT MICE

Author
item NOBEN-TRAUTH, NANCY - NATL INST ALLERGY, MD
item SHULTZ, LEONARD - JACKSON LAB, BAR HARBOR
item BROMBACHER, FRANK - MAX-PLANCK-INST, GERMANY
item Urban, Joseph
item GU, HUA - NATL INST ALLERGY, MD
item PAUL, WILLIAM - NATL INST ALLERGY, MD

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/30/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: We have demonstrated that a naturally occurring molecule produced by animals is able to induce the expulsion of worm parasites from the intestine. This molecule can be used as an adjunct or replacement therapy for chemical control of infections in livestock that often require withdrawal time before meat can be consumed by the public. Knowledge of how this molecules is stimulated to appear during an infection would be useful for designing procedure that enhance its induction during an infection or can be used to design synthetic molecules that mimic the effects of this molecule. This study shows that a unique sub class of cells is first to produce this molecule once the host is infected by the parasite. Scientists will be able to use this information to target the stimulation of this cell population during an infection or as a preventative measure for livestock or humans that are at risk of being infected by worm parasites.

Technical Abstract: Interleukin-4 receptor alpha-chain (IL-4Rà) deficient mice were generated by gene-targeting in BALB/c embryonic stem cells. Mutant mice showed a loss of IL-4 signal transduction and functional activity. The lack of IL- 4Rà resulted in markedly diminished, but not absent, Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis. CD4+, ,CD62L-high and CD62L-low T cell populations from uninfected IL-4Rà-/- mice were isolated by cell sorting. Upon primary stimulation of T cell receptor cross-linkage, the CD62L-low, but not CD62L-high, cells secreted considerable amounts of IL-4, which was strikingly enhanced upon 4-day culture with anti-CD3 in the presence or absence of IL-4. CD62L-low cells isolated from IL-4Rà-/-, á2-microglobulin-/- (á2m) double homozygous mice produced less IL-4 than did either IL-4Rà-/- or wild-type mice. These results indicate that an IL-4-independent, á2m-dependent pathway exists through which the CD62L-low CD4+ population has acquired IL-4-producing capacity in vivo, strongly suggesting that these cells are NK T cells.