Antigen-specific dose-dependent system for the study of an inheritable and reversible phenotype in mouse CD4+ T cells
| Autor: | B Robert Franza, Alexander Y. Rudensky, Raymond K Kong, Eduardo J Firpo, James M. Roberts, Qinghong Zhou |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Cyclin E Cell division Transgene T-Lymphocytes Immunology Dose-Response Relationship Immunologic Cell Cycle Proteins Mice Transgenic Biology Epitopes Mice Antigen Immunology and Allergy Animals Enzyme Inhibitors Receptor Interphase Clonal Anergy Tumor Suppressor Proteins Original Articles Cell cycle Flow Cytometry Phenotype Cell biology Mice Inbred C57BL CD4 Antigens Interleukin-2 Intracellular Cell Division Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Immunology. 107(4) |
| ISSN: | 0019-2805 |
| Popis: | The transgenic T-cell receptor in mouse TEa CD4+ lymphocytes recognizes an endogenous peptide, Ealpha52-68, presented in the context of the major histocompatibility complex class II molecule I-Ab. In response to an optimal peptide concentration TEa cells enter the cell cycle and proliferate. However, a single exposure to high doses of the specific peptide diminished cell expansion upon subsequent restimulation. This hyporesponsive, or anergic, phenotype can still be detected after multiple restimulations indicating that the hyporesponsiveness persists despite cell division and it was inherited by daughter cells. Furthermore, we demonstrated that this hypoproliferative response is associated with high p27Kip1 and cyclin E protein levels, and reduced intracellular interleukin-2 (IL-2) expression. Addition of exogenous IL-2 was required to reset p27Kip1 levels in the progeny derived from hyporesponsive TEa cells. Thus, we have established antigen dose-dependent induction of a reversible, inheritable (i.e. epigenetic) phenotype and we have identified at least three components of the network of interactions: p27Kip1 cyclin E, and IL-2 expression. |
| Databáze: | OpenAIRE |
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