International Immunology, Vol 10, 1777-1788, Copyright © 1998 by Oxford University Press
N Wang, B Wang, M Salio, D Allen, J She and C Terhorst
The TCR-associated CD3 complex consists of four subunits, i.e. CD3gamma,
delta, epsilon and zeta, which are expressed very early in T cell
development prior to the expression of the TCR and the pre-TCR alpha chain.
It is unclear whether the expression of each CD3 protein is independent of,
or is influenced by, other CD3 subunits. To study whether CD3epsilon
regulates expression of CD3gamma and delta genes, we generated a strain of
CD3epsilon-deficient mice termed CD3epsilon(deltaP/deltaP)
(epsilon(deltaP)), in which the promoter of CD3E was disrupted, and
subsequently reconstituted these mice with a CD3epsilon transgene. In the
epsilon(deltaP) mice, T cell development is arrested at the double-negative
stage and targeting the CD3epsilon gene caused severe inhibition of
CD3gamma and delta gene expression. Introduction of the CD3epsilon
transgene did not restore CD3gamma and delta expression. However, a very
small fraction of prothymocytes that expressed CD3gamma and delta was
rescued upon reconstitution of the CD3epsilon transgene. Remarkably, this
rescue led to a very efficient differentiation and maturation of
thymocytes, resulting in a significant T cell population in the periphery.
These results demonstrate that CD3epsilon does not regulate expression of
CD3gamma and delta genes, and underscore the capacity of each prothymocyte
to give rise to a large number of mature peripheral T cells.
ARTICLES
Expression of a CD3epsilon transgene in CD3epsilon(null) mice does not restore CD3gamma and delta expression but efficiently rescues T cell development from a subpopulation of prothymocytes
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
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