| First Author | Waterhouse P | Year | 1997 |
| Journal | Eur J Immunol | Volume | 27 |
| Issue | 8 | Pages | 1887-92 |
| PubMed ID | 9295023 | Mgi Jnum | J:42659 |
| Mgi Id | MGI:1096090 | Doi | 10.1002/eji.1830270811 |
| Citation | Waterhouse P, et al. (1997) Normal thymic selection, normal viability and decreased lymphoproliferation in T cell receptor-transgenic CTLA-4-deficient mice. Eur J Immunol 27(8):1887-92 |
| abstractText | CTLA-4 is a T cell surface receptor essential for the negative regulation of T cell activation. In the CTLA-4-deficient mouse, a dramatic accumulation of activated peripheral T cells effects extensive damage to host tissues, resulting in mortality within 5 weeks of age. To determine whether the accumulation of activated T cells in CTLA-4(-/-) mice is due to a defect in thymic selection, we examined negative selection in CTLA-4(-/-) mice using two transgenic T cell receptor (TCR) models of thymic selection. Neither the H-Y-specific TCR nor the lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic models revealed a defect in positive or negative selection in CTLA-4(-/-) mice in vivo or in vitro. In fact, the negatively selecting phenotype of male H-YTCR-transgenic mice greatly mitigated the accumulation of activated peripheral T cells. Further, peripheral CTLA-4(-/-) T cells expressing a single LMCV-specific transgenic TCR did not have an activated phenotype, indicating that CTLA-4(-/-) T cells require specific antigen for proliferation. These results demonstrate that specific antigen is required for the lymphoproliferation observed in CTLA-4(-/-) mice, and that CTLA-4 deficiency does not lead to a gross defect in negative selection. |
