| First Author | Chan S | Year | 1998 |
| Journal | J Exp Med | Volume | 188 |
| Issue | 12 | Pages | 2321-33 |
| PubMed ID | 9858518 | Mgi Jnum | J:113263 |
| Mgi Id | MGI:3665241 | Doi | 10.1084/jem.188.12.2321 |
| Citation | Chan S, et al. (1998) Visualization of CD4/CD8 T cell commitment. J Exp Med 188(12):2321-33 |
| abstractText | A system to innocuously visualize T cell lineage commitment is described. Using a 'knock-in' approach, we have generated mice expressing a beta-galactosidase reporter in place of CD4; expression of beta-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. |
