Abstract
Abstract Auto-aggressive T cells are responsible for the onset and perpetuation of autoimmune diseases, including Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). A subset of CD4 T cells, CD4+CD40+ (Th40) cells, have an expansive role in the Non-Obese Diabetic (NOD) mouse model of T1D. Not only do Th40 cells increase in number with the onset of disease, but they are necessary and sufficient in transferring T1D from NOD to NOD.scid mice. Because Th40 cells have an imperative role in the development of disease in T1D, we considered that Th40 cells might also be involved in Experimental Autoimmune Encephalomyelitis (EAE), a neurological disease which mimics human MS. When given myelin oligodendrocyte glycoprotein (MOG) and pertussis toxin (PT), C57Bl/6 mice develop neurological symptoms and impaired motor functions similar to those in human MS patients. Data shows an increase, not only in CD4 T cells, but also in Th40 cells in mice receiving induction of EAE. This does not occur in their control counterparts. Further, purified splenic Th40 cells from asymptomatic disease induced C57Bl/6 mice rapidly transfer EAE to C57Bl/6.scid recipients with only 1.2x106 cells, demonstrating that Th40 cells alone can induce EAE. Also, we show cerebral infiltrates of immune cells in localized regions of the brain of the Th40 recipient mice, suggesting that these lesions are similar to the lesions found in human MS patients.
Published Version
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