| First Author | Isakson SH | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 4 | Pages | 1585-93 |
| PubMed ID | 22778392 | Mgi Jnum | J:189759 |
| Mgi Id | MGI:5446965 | Doi | 10.4049/jimmunol.1200342 |
| Citation | Isakson SH, et al. (2012) Spontaneous autoimmunity in the absence of IL-2 is driven by uncontrolled dendritic cells. J Immunol 189(4):1585-93 |
| abstractText | BALB/c IL-2-deficient (IL-2-KO) mice develop systemic autoimmunity, dying within 3 to 5 wk from complications of autoimmune hemolytic anemia. Disease in these mice is Th1 mediated, and IFN-gamma production is required for early autoimmunity. In this study, we show that dendritic cells (DCs) are required for optimal IFN-gamma production by T cells in the IL-2-KO mouse. Disease is marked by DC accumulation, activation, and elevated production of Th1-inducing cytokines. IL-2-KO DCs induce heightened proliferation and cytokine production by naive T cells compared with wild-type DCs. The depletion of either conventional or plasmacytoid DCs significantly prolongs the survival of IL-2-KO mice, demonstrating that DCs contribute to the progression of autoimmunity. Elimination of Th1-inducing cytokine signals (type 1 IFN and IL-12) reduces RBC-specific Ab production and augments survival, indicating that cytokines derived from both plasmacytoid DCs and conventional DCs contribute to disease severity. DC activation likely precedes T cell activation because DCs are functionally activated even in an environment lacking overt T cell activation. These data indicate that both conventional and plasmacytoid DCs are critical regulators in the development of this systemic Ab-mediated autoimmune disease, in large part through the production of IL-12 and type 1 IFNs. |
