Genetic mapping of a marine locus controlling development of T helper 1/T helper 2 type responses

James D. Gorham, Mehmet L. Güler, Robert G. Steen, Aaron J. Mackey, Mark J. Daly, Kathy Frederick, William F. Dietrich, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B10.D2) favoring ThI development and others (e.g., BALB/c) favoring Th2 development. Recently we found that B10.D2 exhibit an intrinsically greater capacity to maintain interleukin 12 (IL-12) responsiveness under neutral conditions in vitro compared with BALB/c T cells, allowing for prolonged capacity to undergo IL-12-induced Th1 development. To begin identification of the loci controlling this genetic effect, we used a T-cell antigen receptor-transgenic system for in vitro analysis of intercrosses between BALB/c and B10.D2 mice and have identified a locus on murine chromosome 11 that controls the maintenance of IL-12 responsiveness, and therefore the subsequent Th1/Th2 response. This chromosomal region is syntenic with a locus on human chromosome 5q31.1 shown to be associated with elevated serum IgE levels, suggesting that genetic control of Th1/Th2 differentiation in mouse, and of atopy development in humans, may be expressed through similar mechanisms.

Original languageEnglish
Pages (from-to)12467-12472
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number22
DOIs
StatePublished - Oct 29 1996

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