| First Author | Bix M | Year | 1998 |
| Journal | J Exp Med | Volume | 188 |
| Issue | 12 | Pages | 2289-99 |
| PubMed ID | 9858515 | Mgi Jnum | J:51707 |
| Mgi Id | MGI:1321474 | Doi | 10.1084/jem.188.12.2289 |
| Citation | Bix M, et al. (1998) Genetic regulation of commitment to interleukin 4 production by a CD4(+) T cell-intrinsic mechanism. J Exp Med 188(12):2289-99 |
| abstractText | The dysregulated expression of interleukin 4 (IL-4) can have deleterious effects on the outcome of infectious and allergic diseases. Despite this, the mechanisms by which naive T cells commit to IL-4 expression during differentiation into mature effector cells remain incompletely defined. As compared to cells from most strains of mice, activated CD4(+) T cells from BALB mice show a bias towards IL-4 production and T helper 2 commitment in vitro 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 proportion of CD4(+) T cells that commit to IL-4 expression. This strain-specific difference in commitment was independent of signals mediated via the IL-4 receptor and hence occurred upstream of potential autoregulatory effects of IL-4. Segregation analysis of the phenotype in an experimental backcross cohort implicated a polymorphic locus on chromosome 16. Consistent with a role in differ-entiation, expression of the phenotype was CD4(+) T cell intrinsic and was evident as early as 16 h after the activation of naive T cells. Probabilistic gene activation is proposed as a T cell-intrinsic mechanism capable of modulating the proportion of naive T cells that commit to IL-4 production. |
