Title

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

UMMS Affiliation

Department of Medicine, Division of Rheumatology

Date

1-1998

Document Type

Article

Medical Subject Headings

Alleles; Animals; B-Lymphocytes; DNA-Binding Proteins; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Interleukin-4; Liver; Lymphocyte Activation; Lymphoid Tissue; Mice; Mice, Inbred BALB C; NFATC Transcription Factors; *Nuclear Proteins; Phenotype; Recombinant Fusion Proteins; T-Lymphocytes; Transcription Factors

Disciplines

Immunology and Infectious Disease

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.

Rights and Permissions

Citation: Immunity. 1998 Jan;8(1):125-34.

Comments

At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

9462518