encephalomyelitis (EAE), activated CD4+ T cells with upregulated IL-2R
mediate inflammation and demyelination in the central nervous system
(CNS). DAB389IL-2, a chimeric fusion protein of IL-2 and
diphtheria toxin, inhibits human and rodent IL-2 activated T cells that
express the high affinity interleukin-2 receptor. In the present study,
DAB389IL-2 was used to treat rats with EAE. We wanted to investigate the possibility that DAB389IL-2 could prevent tissue destruction within the CNS. We used a suboptimal dose of DAB389IL-2 that allowed substantial transmigration of inflammatory cells across the blood-brain barrier. DAB389IL-2 inhibited infiltration of CD4+, CD8+, CD25+ and TCR αβ+
associated mononuclear cells and inflammatory macrophages in the spinal
cord on day 13 post-immunization, at the peak of disease. Gene
expression study showed that DAB389IL-2 treatment suppressed
TNF-α and IFN-γ as well as IL-10 cytokine gene expression in the spinal
cord of rats with EAE on day 13. DAB389IL-2 in vitro
treatment suppressed cytotoxicity of MBP-activated T cells from rats
with EAE against oligodendrocytes in culture by 66%. Astrocytes were
less targeted by MBP activated T cells in vitro. This study suggests
that DAB389IL-2 directly targets CD4+ and CD25+ (IL-2R) T cells and effector T cell function and also indirectly suppresses the activation of macrophage CD169+ (ED3+) and microglia CD11b/c (OX42+) populations in the CNS.
Well this is another installment of this approach
Phillips SM, Bhopale MK, Constantinescu CS, Ciric B, Hilliard B, Ventura E, Lavi E, Rostami A. Effect of DAB(389)IL-2 immunotoxin on the course of experimental autoimmune encephalomyelitis in Lewis rats. J Neurol Sci. 2007; 263(1-2):59-69.
Phillips SM, Bhopale MK, Hilliard B, Zekavat SA, Ali MA, Rostami A. Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2 receptor targeted fusion toxin, DAB(389)IL-2. Cell Immunol. 2010;261(2):144-52
Is the dogma right?