| First Author | Prinz I | Year | 2004 |
| Journal | Gastroenterology | Volume | 126 |
| Issue | 1 | Pages | 170-81 |
| PubMed ID | 14699498 | Mgi Jnum | J:87207 |
| Mgi Id | MGI:2683874 | Doi | 10.1053/j.gastro.2003.10.062 |
| Citation | Prinz I, et al. (2004) Exacerbated colitis associated with elevated levels of activated CD4+ T cells in TCRalpha chain transgenic mice. Gastroenterology 126(1):170-81 |
| abstractText | Background & Aims: An unconventional CD4+ TCRalpha(-)beta(+) cell population mediates the development of colitis resembling ulcerative colitis in T-cell receptor alpha mutant (TCRalpha(-/-)) mice. However, the significance of such T cells in individuals with an intact TCRalpha locus remains unclear. Because a substantial proportion of naturally rearranged TCRalpha chains fails to pair with TCRbeta chains, the aim of this study was to analyze the development of CD4+ TCRalpha(-)beta(+) cells and the course of colitis in the presence of such a TCRalpha chain. Methods: TCR chain transgenic TCRalpha(-/-) mice were generated and compared with wild-type and TCRalpha(-/-) mice by flow cytometric analysis of T lymphocytes with respect to their TCR expression and activation status and by histological analysis of colon tissue. The colitogenic potential of the unconventional CD4+ TCRalpha(-)beta(+) cells was assessed by adoptive transfer experiments. Furthermore, the half-life of TCRbeta chains was determined by pulse-chase labeling and immunoprecipitation. Results: Transgenic expression of a TCR Valpha7.2 chain led to increased frequencies of CD4+ TCRalpha(-)beta(+) cells that caused rapid onset of colitis, reminiscent of, but even more severe than, that in TCRalpha(-/-) mice. This unconventional T-cell population displayed a constitutively activated phenotype in normal and transgenic TCRalpha(-/-) mice. An extended half-life of newly synthesized TCRbeta chains suggests a chaperone function of the TCR Valpha7.2 chain in TCRalpha(-/-) mice. Conclusions: Physiological TCRalpha rearrangement can promote the formation of chronically activated CD4+ TCRalpha(-)beta(+) T cells and may play a role in the etiology of UC. |
