Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice

Immunity. 1996 Apr;4(4):397-405. doi: 10.1016/s1074-7613(00)80253-8.


NF-ATp is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In this study, we show that mice with a null mutation in the NF-ATp gene have splenomegaly with hyperproliferation of both B and T cells. They also display early defects in the transcription of multiple genes encoding cytokines and cell surface receptors, including CD40L and FasL. A striking defect in early IL-4 production was observed after ligation of the TCR complex by treatment with anti-CD3 in vivo. The transcription of other cytokines including IL-13, GM-CSF, and TNF alpha was also affected, though to a lesser degree. Interestingly, the cytokines IL-2 and IFN gamma were minimally affected. Despite this early defect in IL-4 transcription, Th2 development was actually enhanced at later timepoints as evidenced by increased IL-4 production and IgE levels in situations that favor the formation of Th2 cells both in vitro and in vivo. These data suggest that NF-ATp may be involved in cell growth, and that it is important for the balanced transcription of the IL-4 gene during the course of an immune response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Base Sequence
  • CD40 Ligand
  • Cell Division
  • DNA Primers / genetics
  • DNA-Binding Proteins
  • Fas Ligand Protein
  • Gene Expression
  • Gene Targeting
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / genetics
  • Killer Cells, Natural / immunology
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Splenomegaly / genetics
  • Splenomegaly / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Th2 Cells / pathology
  • Transcription Factors / deficiency*


  • DNA Primers
  • DNA-Binding Proteins
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • NFATC Transcription Factors
  • Nfatc2 protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • CD40 Ligand
  • Interleukin-4