CD4 super(+) T cells from IRF-1-deficient mice exhibit altered patterns of cytokine expression and cell subset homeostasis

Interferon regulatory factor-1 (IRF-1) is a member of a family of transcription factors that regulate an array of genes involved in cell growth, differentiation, and death. Analysis of cytokine expression by stimulated CD4 super(+) cells from IRF-1 super(-/-) and IRF-1 super(+/+) mice revealed that IRF-1 deficiency resulted in an elevated production of Th2-related cytokines and a compensatory decrease in the expression of naive cell- and Th1-related cytokines. The altered cytokine profiles of IRF-1 super(-/-) cells could be explained, in part, by a shift in the representation of subsets of CD4 super(+) cells; IRF-1 super(-/-) mice exhibited a decreased percentage of naive cells (a major source of IL-2) but increased numbers of memory or effector cells (the source of Th2-related cytokines). We analyzed purified, phenotypically matched memory /effector cells from IRF-1 super(-/-) and IRF-1 super(+/+) mice and found that the increased Th2:Th1 cytokine ratio was still evident in the IRF-1 super(-/-) group, thus suggesting that IRF-1 is involved in the polarization of the cytokine repertoire in CD4 super(+) cells. Our data indicate that IRF-1 plays an important role in the maintenance of CD4 super(+) cell subset homeostasis and in the expression of cytokines by naive and memory/effector cells.