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J. Exp. Med.,
Volume 188, Number 12, December 21, 1998 2321-2333
By
From the Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP),
Strasbourg, 67404 Illkirch Cedex, France
A system to innocuously visualize T cell lineage commitment is described. Using a "knock-in"
approach, we have generated mice expressing a 
-galactosidase reporter in place of CD4; expression of -galactosidase in these animals appears to be an accurate and early indicator of
CD4 gene transcription. We have exploited this knock-in line to trace CD4/CD8 lineage
commitment in the thymus, avoiding important pitfalls of past experimental approaches. Our
results argue in favor of a selective model of thymocyte commitment, demonstrating a fundamentally symmetrical process: engagement of either class of major histocompatibility complex
(MHC) molecule by a differentiating CD4+CD8+ cell can give rise to T cell antigen receptor
(TCR)hi thymocytes of either lineage. Key findings include (a) direct demonstration of a substantial number of CD4-committed, receptor/coreceptor-mismatched cells in MHC class II-
deficient mice, a critical prediction of the selective model; (b) highly efficient rescue of such
"mismatched" intermediates by forced expression of CD8 in a TCR transgenic line, and an explanation of why previous experiments of this nature were less successful
a major past criticism of the selective model; (c) direct demonstration of an analogous, though smaller, population of CD8-committed mismatched intermediates in class I-deficient animals. Finally, we
found no evidence of a CD4 default pathway.
-galactosidase
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