Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc

Immunity. 1998 Jan;8(1):125-34. doi: 10.1016/s1074-7613(00)80465-3.

Abstract

The NF-AT family of transcription factors activates early immune response genes such as cytokines. In the adult, NF-ATc is expressed exclusively in the lymphoid system and is induced upon lymphocyte activation. NF-ATc null mutant mice die in utero of cardiac failure, precluding analysis of the role of NF-ATc in lymphocyte activation. By using RAG-2-deficient blastocyst complementation, we now demonstrate that young, highly chimeric mice lacking NF-ATc have impaired repopulation of both thymus and peripheral lymphoid organs. Furthermore, NF-ATc deficiency impaired T lymphocyte activation and secretion of IL-4. B lymphocytes displayed reduced proliferation and a selective loss of IL-4-driven immunoglobulin isotypes both in vivo and in vitro. Our data demonstrate that NF-ATc is essential for the optimal generation and function of mature T and B lineage cells, with an especially profound effect on IL-4-driven responses.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin M / biosynthesis
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / physiology*
  • Liver / embryology
  • Liver / physiology
  • Lymphocyte Activation / immunology
  • Lymphoid Tissue / cytology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / physiology*
  • Mice
  • Mice, Inbred BALB C
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phenotype
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • Immunoglobulin G
  • Immunoglobulin M
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Rag2 protein, mouse
  • Recombinant Fusion Proteins
  • Transcription Factors
  • V(D)J recombination activating protein 2
  • Interleukin-4
  • Immunoglobulin E