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B in T-Lineage Cells Leads to a Dramatic Decrease in Cell Proliferation and Cytokine Production and to Increased Cell Apoptosis in Response to Mitogenic Stimuli, But Not to Abnormal Thymopoiesis1
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Laboratoire d’Immunologie Cellulaire et Tissulaire, Centre National de la Recherche Scientifique UMR 7627, Batiment Centre d’Etudes et de Recherches Virologiques et Immunologiques, Hôpital de la Pitié-Salpêtrière, Paris, France;
Unit of Molecular Genetics, DIBIT, Hospital San Raffaele, Milan, Italy; and
Institut National de la Santé et Research Médicale, Unit 25, Hôpital Necker Enfants Malades, Paris, France
To understand the role of NF-
B complexes in T cell development
and activation, we have generated transgenic mice in which RelA and
c-Rel complexes were selectively inhibited in the T-lineage cells by
specific expression of a trans-dominant form of
IB
. Transgene expression did not affect the thymic development,
but led to lowered numbers of splenic T cells and to a dramatic
decrease in the ex vivo proliferative response of splenic T
lymphocytes. Analysis of IL-2 and IL-2R expression demonstrated that
the perturbation of the proliferation response was not attributable to
an abnormal expression of these genes. In contrast, expression of IL-4,
IL-10, and IFN-
was strongly inhibited in the transgenic T cells.
The proliferative deficiency of the transgenic T cells was associated
with an increased apoptosis. These results point out the involvement of
NF-B/Rel family proteins in growth signaling pathways by either
regulating proteins involved in the IL-2 signaling or by functionally
interfering with the cell cycle progression.
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