Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads to severely compromised development of natural killer and T helper type 1 cells
M. Lohoff et al., Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads to severely compromised development of natural killer and T helper type 1 cells, J EXP MED, 192(3), 2000, pp. 325-335
Interferon (IFN) regulatory factor (IRF)-2 was originally described as an a
ntagonist of IRF-1-mediated transcriptional regulation of-IFN-inducible gen
es. IRF-1(-/-) mice exhibit defective T helper type 1 (Th1) cell differenti
ation. We have used experimental leishmaniasis to show that, like IRF-1-/-
mice, IRF-2(-/-) mice are susceptible to Leishmania major infection due to
a de feet in Th1 differentiation. Natural killer (NK) cell development is c
ompromised in both IRF-1(-/-) and IRF-2-/- mice, but the underlying mechani
sm differs. NK (but not NK+ T) cell numbers are decreased in IRF-2-/- mice,
and the NK cells that are present are immature in phenotype. Therefore, li
ke IRF-1, IRF-2 is required for normal generation of Th1 responses and for
NK cell development in vivo. In this particular circumstance the absence of
IRF-2 cannot be compensated for by the presence of IRF-1 alone. Mechanisti
cally, IRF-2 may act as a functional agonist rather than antagonist of IRF-
1 for some, but not all, IFN-stimulated regulatory element (ISRE)-responsiv
e genes.