| First Author | Chen YT | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 5 | Pages | 1928-1943 |
| PubMed ID | 28108557 | Mgi Jnum | J:244717 |
| Mgi Id | MGI:5913496 | Doi | 10.4049/jimmunol.1600967 |
| Citation | Chen YT, et al. (2017) Low-Level MHC Class II Expression Leads to Suboptimal Th Cell Response, Increased Autoaggression, and Heightened Cytokine Inducibility. J Immunol 198(5):1928-1943 |
| abstractText | The development and activation of MHC class II (MHC-II)-restricted CD4+ T cells are distinct immunological processes that are strictly MHC-II-dependent. To address their relative dependence on MHC-II, we established a novel ENU-induced mutant mouse on the C57BL/6 background, named I-A12%, with approximately 8-fold reduced I-A expression on the surface of B cells, dendritic cells, cortical thymic epithelial cells, and medullary thymic epithelial cells. I-A100% and I-A12% mice are highly similar with respect to the numbers of double-positive thymocytes, CD4+CD8- T cells, regulatory T cells, CD4+ T cell marker expression, lifespan, and Th/regulatory T cell function. Despite the demonstration of functional intrathymic negative selection in I-A12% mice, transfer of I-A12% CD25-CD4+ T cells into RAG-knockout hosts revealed increased autoaggression activity against the liver. Compared to I-A100% mice, infection of I-A12% mice with graded doses of Listeria monotcytogenes or influenza virus revealed comparable and significantly reduced generation of Ag-specific CD4+ T cells at high and low infection doses, respectively. A significantly weakened Ag-specific recall cytokine production response was also found for I-A12% mice previously infected with a relative low dose of L. monocytogenes CD44hiCD4+ T cells from I-A100% and I-A12% mice previously infected with a relatively high L. monocytogenes dose displayed highly similar Ag-specific multicytokine production profiles. In contrast, polyclonal activation of endogenous memory-like I-A12% CD44hiCD4+ T cells revealed highly elevated production of multiple cytokines. Our results demonstrate that there exist distinct thresholds for different MHC-II-dependent immunological processes. The I-A12% mutant mouse model we describe in the present study is a valuable tool for investigations on the quantitative cause-effect relationship in MHC-II-dependent normal and autoimmune responses. |
