International Immunology, Vol 9, 179-187, Copyright © 1997 by Oxford University Press
Y Uematsu, A Donda and G De Libero
We analyzed the activity of the enhancer, the promoter and the silencer of
the human CD4 gene during T cell development using transgenic mice.
Immunofluorescence studies on thymic populations of mice carrying
transgenes in various combinations of these regulatory DNA elements
revealed that thymocytes control the CD4 gene in a different manner than
mature peripheral T lymphocytes. The 5'-positive regulatory unit,
consisting of the promoter and the 5' enhancer, is already active at the
CD4-CD8-double-negative (DN) stage of development. However, its activity
becomes lower in the double-positive and a fraction of the CD4+ CD8int/-
cell population, indicating that an additional enhancer, located in either
the first or the third intron of the CD4 gene, is required for CD4 gene
expression in this population. The other studied regulatory element is the
minimal CD4 silencer which inhibits CD4 gene expression in peripheral CD8 T
lymphocytes. This silencer is inactive in the most immature DN thymocytes,
which probably use a distinct silencer mechanism to down-regulate CD4 gene
expression. Unexpectedly, the CD4 silencer is also active in CD4+ CD8int/-
cells of the thymus, implying that an anti-silencer may be required to
resume CD4 expression in this cell population. Altogether, the CD4 gene is
regulated by several positive and negative regulatory mechanisms which come
into play in a developmentally coordinated manner.
ARTICLES
Thymocytes control the CD4 gene differently from mature T lymphocytes
Department of Research, University Hospital, Basel, Switzerland.
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