Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses.
Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B10.D2) favoring Th1 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.
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J D
JD
Gorham
M L
ML
Güler
R G
RG
Steen
A J
AJ
Mackey
M J
MJ
Daly
K
K
Frederick
W F
WF
Dietrich
K M
KM
Murphy
D000818:Animals; D002874:Chromosome Mapping; D002875:Chromosomes / Q000737:chemistry; D002895:Chromosomes, Human, Pair 5; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D018417:Th1 Cells / Q000166:cytology*; D018418:Th2 Cells / Q000166:cytology*
D018664:Interleukin-12