Saturday, 11 May 2013

Another new model for monitoring immune effects of MS

Zayoud M, El Malki K, Frauenknecht K, Trinschek B, Kloos L, Karram K, Wanke F, Georgescu J, Hartwig UF, Sommer C, Jonuleit H, Waisman A, Kurschus FC. Subclinical CNS Inflammation as Response to a Myelin Antigen in Humanized Mice. J Neuroimmune Pharmacol. 2013 May. [Epub ahead of print]

Multiple sclerosis is a demyelinating autoimmune disease of the CNS. Its animal model experimental autoimmune encephalomyelitis is commonly induced by active immunization with myelin antigens. To investigate human immune responses against myelin antigens in vivo we established a new subclinical experimental autoimmune encephalomyelitis model in humanized mice. NOD/Scidγc-/- animals were transferred with peripheral blood mononuclear cells from healthy human donors and immunized with myelin antigens in complete Freund's adjuvant and antigen-pulsed autologous dendritic cells. Human T cells recovered from these animals reacted specifically to the soluble domain of myelin oligodendrocyte glycoprotein and secreted proinflammatory cytokines. Furthermore, immunized animals developed subclinical CNS inflammation with infiltrating CD4+ and CD8+ T cells and production of encephalitogenic cytokines. Thus, this model of myelin-induced CNS inflammation by human T cells may allow testing of new human-specific therapeuticals for multiple sclerosis.

SCID (severe combine immunodeficiency mice) lack T and B cells and so they can have a transfusion of human cells and they the mice do not reject them. The common gamma chain receptor (γc, also referred to as the IL-2receptor gamma chain) is a component of the IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors and is the gene involved in X-linked SCID. The addition of the γc mutation to the NOD/SCID backgrounds further blocks T and B cell development due toa lack of IL-2 (growth factor) signaling and also prevents maturation and expansion of Natural killer cells cells via a lack of IL-15 signaling. These mice were loaded with human cells and the responsiveness to myelin antigens were found.  Maybe it could be used to assesss therapies.

This mouse could be supplemented with transgenes for major histocompatibility complex antigen and human CD4 and CD8 and then the recognition antigens may be even more relevant.

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