Great stuff Bromley. This sounds like a significant step in unravelling MS. I looked around a little for more on the IL2R and IL7R and came up with a few things:
This June 2007 presentation from UCSF on MS genetics (IL7R stuff starts on slide #30)
http://www.mscare.org/cmsc/images/pdf/2 ... Hauser.pdf
The abstract below includes a connection between IL2R and FoxP3 t-cells, which are connected to how Neurovax is supposed to work, so I'm suddenly more interested in Neurovax.
Selective availability of IL-2 is a major determinant controlling the production of CD4+CD25+Foxp3+ T regulatory cells.
J Immunol. 2006 Oct 15;177(8):5115-21.
Yu A, Malek TR.
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
The development and maintenance of T regulatory (Treg) cells critically depend on IL-2. This requirement for IL-2 might be due to specificity associated with IL-2R signal transduction or because IL-2 was uniquely present in the niche in which Treg cells reside. To address this issue, we examined the capacity of IL-7R-dependent signaling to support Treg cell production and prevent autoimmunity in IL-2Rbeta(-/-) mice. Expression of transgenic wild-type IL-7R or a chimeric receptor that consisted of the extracytoplasmic domain of the IL-7R alpha-chain and the cytoplasmic domain of IL-2R beta-chain in IL-2Rbeta(-/-) mice did not prevent autoimmunity. Importantly, expression of a chimeric receptor that consisted of the extracytoplasmic domain of the IL-2R beta-chain and the cytoplasmic domain of IL-7R alpha-chain in IL-2Rbeta(-/-) mice led to Treg cells production in the thymus and periphery and prevented autoimmunity. Signaling through the IL-2R or chimeric IL-2Rbeta/IL-7Ralpha in vivo or the culture of thymocytes from IL-2Rbeta(-/-) mice with IL-7 led to up-regulation of Foxp3 and CD25 on Treg cells. These findings indicate that IL-7R signal transduction is competent to promote Treg cell production, but this signaling requires triggering through IL-2 by binding to the extracytoplasmic portion of the IL-2R via this chimeric receptor. Thus, a major factor controlling the nonredundant activity of the IL-2R is selective compartmentalization of IL-2-producing cells with Treg cells in vivo.
Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7R alpha-expressing cells.
J Exp Med. 2007 Mar 19;204(3):547-57. Epub 2007 Feb 20.
Dooms H, Wolslegel K, Lin P, Abbas AK.
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
The common gamma chain cytokines interleukin (IL)-2 and IL-7 are important regulators of T cell homeostasis. Although IL-2 is implicated in the acute phase of the T cell response, IL-7 is important for memory T cell survival. We asked whether regulated responsiveness to these growth factors is determined by temporal expression of the cytokine-specific IL-2 receptor (R) alpha and IL-7Ralpha chains. We demonstrate that IL-2Ralpha is expressed early after priming in T cell receptor-transgenic CD4(+) T cells, whereas IL-7Ralpha expression is lost. In the later stage of the response, IL-7Ralpha is reexpressed while IL-2Ralpha expression is silenced. This reciprocal pattern of IL-2Ralpha/IL-7Ralpha expression is disturbed when CD4(+) T cells are primed in the absence of IL-2 signals. Primed IL-2(-/-) or CD25(-/-) (IL-2Ralpha(-/-)) CD4(+) T cells, despite showing normal induction of activation markers and cell division, fail to reexpress IL-7Ralpha late in the response. Because the generation of CD4(+) memory T cells is dependent on IL-7-IL-7Ralpha interactions, primed IL-2(-/-) or CD25(-/-) CD4(+) T cells develop poorly into long-lived memory cells. Retrovirus-mediated expression of IL-7Ralpha in IL-2(-/-) T cells restores their capacity for long-term survival. These results identify IL-2 as a factor regulating IL-7Ralpha expression and, consequently, memory T cell homeostasis in vivo.