| First Author | Guiducci C | Year | 2005 |
| Journal | Eur J Immunol | Volume | 35 |
| Issue | 2 | Pages | 557-67 |
| PubMed ID | 15682445 | Mgi Jnum | J:95614 |
| Mgi Id | MGI:3526629 | Doi | 10.1002/eji.200425810 |
| Citation | Guiducci C, et al. (2005) CD40/CD40L interaction regulates CD4(+)CD25(+) T reg homeostasis through dendritic cell-produced IL-2. Eur J Immunol 35(2):557-67 |
| abstractText | CD4(+)CD25(+) regulatory T cells (T reg) development and homeostasis require IL-2 and costimulation through same TNF-receptor family members. CD40KO mice have reduced number of T reg in peripheral blood, thymus and spleen. Herein we show that naive T reg express low basal level of CD40L that is upregulated upon TCR-triggered mediated activation. Treatment of wt mice with Ab blocking CD40/CD40L interaction results in a fast decrease in T reg number that rapidly recovers upon Ab withdrawal. CFSE-labeled T reg from wt mice injected into CD40KO, but not wild-type (wt) mice, showed reduced survival and proliferation in homeostatic setting. In vitro, dendritic cells from CD40KO mice but not wt mice produce diminished amount of IL-2 upon T reg encounter and are impaired in expanding T reg, a defect corrected by the addition of rIL-2. Accordingly, four daily IL-2 administrations to CD40KO mice normalize T reg number by promoting both their survival and homeostatic proliferation. Such IL-2 effect is transient since T reg number returns to the low constitutive level described in CD40KO mice within 5 days upon IL-2 withdrawal thus suggesting that IL-2 is persistently needed to assure T reg homeostasis. |
