MULTISTAGE REGULATION OF TH1-TYPE IMMUNE-RESPONSES BY THE TRANSCRIPTION FACTOR IRF-1

Eradication of a given pathogen is dependent on the selective differen tiation of T helper (Th) cells into Th1 or Th2 types. We show here tha t T cells from mice lacking the transcription factor IRF-1 fail to mou nt Th1 responses and instead exclusively undergo Th2 differentiation i n vitro. Compromised Th1 differentiation is found to be associated wit h defects in multiple cell types, namely impaired production of interl eukin-12 by macrophages, hyporesponsiveness of CD4(+) T cells to inter leukin-12, and defective development of natural killer cells. These re sults indicate the involvement of IRF-1 in multiple stages of the Th1 limb of the immune response.