| First Author | DeRyckere D | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 2 | Pages | 647-55 |
| PubMed ID | 16002659 | Mgi Jnum | J:101673 |
| Mgi Id | MGI:3604441 | Doi | 10.4049/jimmunol.175.2.647 |
| Citation | DeRyckere D, et al. (2005) E2F1 and E2F2 are differentially required for homeostasis-driven and antigen-induced T cell proliferation in vivo. J Immunol 175(2):647-55 |
| abstractText | Homeostasis-driven T cell proliferation occurs in response to a lymphopenic environment and is mediated by TCR and IL-7 signaling. In this report, we demonstrate a defect in the proliferation of murine naive and memory T cells lacking both E2F1 and E2F2 in response to lymphopenic conditions, suggesting that E2F1 and E2F2 function redundantly downstream of TCR and/or IL-7 signaling during homeostasis-driven proliferation. In contrast, T cell proliferation in response to antigenic stimulation is either unaffected (in vivo) or potentiated (ex vivo) by loss of E2F1 and E2F2, indicating divergent requirements for these E2F factors in T cell proliferation mediated by distinct stimuli. E2F1/E2F2 double knockout (DKO) T cells enter S phase in response to homeostatic signaling, but fail to divide, suggesting that S phase progression is either incomplete or defective. In addition, E2F1/E2F2 DKO mice do not recover normal T cell numbers following exposure to a sublethal dose of radiation, indicating that this defect in homeostasis-driven proliferation is physiologically relevant. Consistent with their failure in cell cycle progression, the differentiation of DKO T cells into memory T cells in response to homeostatic signals is significantly reduced. These observations support the idea that proliferation is required for memory T cell formation and also have implications for the development of clinical strategies to minimize the occurrence of lymphopenia-induced autoimmunity. |
