| First Author | Osborne LC | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 4 | Pages | 1981-8 |
| PubMed ID | 21239710 | Mgi Jnum | J:169162 |
| Mgi Id | MGI:4939963 | Doi | 10.4049/jimmunol.1002224 |
| Citation | Osborne LC, et al. (2011) Elevated IL-7 availability does not account for T cell proliferation in moderate lymphopenia. J Immunol 186(4):1981-8 |
| abstractText | Lymphopenia-induced proliferation (LIP) is a proliferative program initiated in response to T cell insufficiency caused by acute or chronic immunodepletion. Studies of lymphopenic mice have demonstrated that the cytokine IL-7 and TCR signaling are critical for LIP. We examined how these two factors impact T cell proliferation following transfer into moderately lymphopenic mice. In this study, we show that moderate lymphopenia ( approximately 25% of wild-type lymphocytes) of IL-7Ralpha knock-in mutant (IL-7Ralpha(449F)) mice supports T cell proliferation, although with decreased frequency and kinetics compared with cells transferred to severely lymphopenic (5% of wild-type lymphocytes) IL-7Ralpha(-/-) hosts. Although previous studies have demonstrated that elevated IL-7 levels play an important role in LIP, IL-7 availability was not elevated in IL-7Ralpha(449F) mice. However, moderate lymphopenia increased access of transferred T cells to self-peptide presented on APCs that can trigger TCR signaling and proliferation. Importantly, we did not detect significant changes in TCR Vbeta usage of proliferated T cells recovered from either moderately or severely lymphopenic hosts. Our work demonstrates that polyclonal T cells retain a diverse TCR repertoire following proliferation mediated by either self-peptide-MHC interaction alone or in combination with IL-7, and that T cell reconstitution is most efficient in the presence of increased IL-7 availability. |
