M. Bix et al., Genetic regulation of commitment to interleukin 4 production by a CD4(+) Tcell-intrinsic mechanism, J EXP MED, 188(12), 1998, pp. 2289-2299
The dysregulated expression of interleukin 4 (IL-4) can have deleterious ef
fects on the outcome of infectious and allergic diseases. Despite this, the
mechanisms by which naive T cells commit to IL-4 expression during differe
ntiation into mature effector cells remain incompletely defined. As compare
d to cells from most strains of mice, activated CD4(+) cells from BALB mice
show that a bias towards IL-4 production and T helper 2 commitment in vitr
o and in vivo. Here, we show that this bias arises not from an increase in
the amount of IL-4 produced per cell, but rather from an increase in the pr
oportion of CD4(+) T cells that commit to IL-4 expression. This strain-spec
ific difference in commitment was independent of signals mediated via the I
L-4 receptor and hence occurred upstream of potential autoregulatory effect
s of IL-4. Segregation analysis of the phenotype in an experimental backcro
ss cohort implicated a polymorhpic locus on chromosome 16. Consistent with
a role in differentiation, expression of the phenotype was CD4(+) T cell in
trinsic and was evident as early as 16 h after the activation of naive T ce
lls. Probabilistic gene activation is proposed as a T cell-intrinsic mechan
ism capable of modulating the proportion of naive T cells that commit to IL
-4 production.