c-Rel is crucial for lymphocyte proliferation but dispensable for T cell effector function.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

c-Rel is crucial for lymphocyte proliferation but dispensable for T cell effector function.

Int Immunol. 1999 Mar;11(3):361-71. Unique Identifier : AIDSLINE MED/99236837
Liou HC; Jin Z; Tumang J; Andjelic S; Smith KA; Liou ML; Cornell University Medical College, Department of Medicine, New; York, NY 10021, USA.

Abstract: The TCR signals are essential for T cell activation and proliferation, primarily through the induction of cytokine and cytokine receptors. Several transcription factor families, including NF-kappaB/Rel, have been implicated in the regulation of cytokine gene expression in T cells in response to antigen, cytokine and mitogenic stimulation. In this study, we show that the mice with a null mutation in the lymphoid-specific c-Rel gene have normal development of lymphoid tissues and T cell compartment. However, T cells derived from the c-Rel knockout mice have several functional abnormalities. The c-Rel-deficient T lymphocytes fail to respond to activation and proliferation signals mediated by the TCR and mitogens in vitro. This is attributed to an impaired production of cytokines IL-2, IL-3 and granulocyte macrophage colony stimulating factor. In addition, the induction of IL-2R alpha chain is impaired in the c-Rel(-/-) T cells. The poor expression of cytokines and IL-2R alpha chain correlates with a reduced nuclear translocation of NF-kappaB components in c-Rel(-/-) T cells. Since activation is prerequisite for differentiation into effector cells, c-Rel(-/-) T cells failed to differentiate into cytotoxic T cells or Th cells without rescuing cytokines. However, upon supplement with exogenous IL-2, the c-Rel(-/-) cytotoxic T lymphocytes are able to execute cytotoxicity and the c-Rel(-/-) Th cells are capable of providing help to normal B cells. These data suggest that c-Rel is important for inducible cytokine and cytokine receptor expression, and a key regulator of early activation and proliferation in T cells.

Keywords: JOURNAL ARTICLE Animal Biological Transport Comparative Study Cytokines/BIOSYNTHESIS *Cytotoxicity, Immunologic CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Gene Targeting *Lymphocyte Transformation Mice Mice, Knockout Mutagenesis, Site-Directed NF-kappa B/METABOLISM Proto-Oncogene Proteins/DEFICIENCY/*GENETICS/METABOLISM *Proto-Oncogenes Receptors, Interleukin-2/BIOSYNTHESIS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes/*IMMUNOLOGY T-Lymphocytes, Helper-Inducer/IMMUNOLOGY
990930
A9991310

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