| First Author | McGargill MA | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 11 | Pages | 7593-605 |
| PubMed ID | 19017948 | Mgi Jnum | J:142202 |
| Mgi Id | MGI:3820727 | Doi | 10.4049/jimmunol.181.11.7593 |
| Citation | McGargill MA, et al. (2008) Drak2 regulates the survival of activated T cells and is required for organ-specific autoimmune disease. J Immunol 181(11):7593-605 |
| abstractText | Drak2 is a serine/threonine kinase expressed in T and B cells. The absence of Drak2 renders T cells hypersensitive to suboptimal stimulation, yet Drak2(-/-) mice are enigmatically resistant to experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. We show in this study that Drak2(-/-) mice were also completely resistant to type 1 diabetes when bred to the NOD strain of mice that spontaneously develop autoimmune diabetes. However, there was not a generalized suppression of the immune system, because Drak2(-/-) mice remained susceptible to other models of autoimmunity. Adoptive transfer experiments revealed that resistance to disease was intrinsic to the T cells and was due to a loss of T cell survival under conditions of chronic autoimmune stimulation. Importantly, the absence of Drak2 did not alter the survival of naive T cells, memory T cells, or T cells responding to an acute viral infection. These experiments reveal a distinction between the immune response to persistent self-encoded molecules and transiently present infectious agents. We present a model whereby T cell survival depends on a balance of TCR and costimulatory signals to explain how the absence of Drak2 affects autoimmune disease without generalized suppression of the immune system. |
