Contributions
Abstract: P1875
Type: Poster
Abstract Category: Late breaking news
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is an animal disease that in part recapitulates the immunopathogenesis of MS. However, most current EAE models display an acute monophasic or non-remitting chronic disease course that does not reflect human MS. When immunized with the encephalitogenic peptide myelin oligodendrocyte glycoprotein 35-55 (MOG[35-55]), mice of the non-obese diabetic (NOD) genetic background develop a paralytic disease characterized by repeated relapses and remissions, which is followed by a chronic phase, a disease course that more closely reflects MS. We therefore exploited a MOG[35-55]-specific T cell receptor transgenic mouse strain on the NOD background, called 1C6, to determine whether adoptive transfer of myelin-specific CD4+ T cells to NOD background mice can invoke an RR-SP disease course. 1C6 CD4+ T cells were differentiated into Th1 or Th17 subsets that were adoptively transferred to NOD.Scid recipient mice, which we monitored for signs of EAE over the course of 100 days. Female Th1 recipients developed EAE with a day of onset (DOO) of 17 +/- 1.4 and a mean disease severity (MDS) of 2.2 +/- 0.2, while Th17 recipients developed EAE with DOO 10.5 +/- 1 and MDS 3 +/- 0.2. Both Th1 and Th17 recipients displayed leukocytic infiltration, demyelination and partial axonal preservation in the brainstem and spinal cord. However, recipients of female Th1 or Th17 cells never experienced a chronically worsening SP phase. By contrast, both male 1C6 Th1 recipients (DOO of 9.7 +/- 0.5, MDS of 3.4 +/- 0.1) and Th17 recipients (DOO of 7.3 +/- 0.6, MDS of 5.0 +/- 0) showed highly severe EAE. Male Th17 recipients displayed a RR-SP disease course that resulted in 100% mortality by d50. No significant differences in the frequency of IFN-gamma-positive or IL-17A-positive CNS-infiltrating CD4+ T cells were observed between males and females; intriguingly, male Th1 recipients displayed significantly fewer TNF-alpha-positive (p< 0.0001) CNS-infiltrating T cells, while male Th17 recipients showed significantly fewer GM-CSF-positive T cells (p< 0.05). These data demonstrate that male sex is an aggravating factor in an adoptive transfer model of EAE on the NOD strain, potentially via effects on innate immune cells or the CNS compartment.
Disclosure: Prenitha Mercy Ignatius Arokia Doss: nothing to disclose.
Asmita Yeola: nothing to disclose.
Joanie Baillargeon: nothing to disclose.
Hans Lassmann: nothing to disclose.
Ana Anderson: nothing to disclose.
Manu Rangachari: invited speaker, EMD Serono, Canada and Biogen Canada; preceptorship, Hoffmann-La Roche, Ltd; recipient of an unrestricted Transitional Career Development Award from EMD Serono, Canada and the endMS Network (2011-2016).
Abstract: P1875
Type: Poster
Abstract Category: Late breaking news
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is an animal disease that in part recapitulates the immunopathogenesis of MS. However, most current EAE models display an acute monophasic or non-remitting chronic disease course that does not reflect human MS. When immunized with the encephalitogenic peptide myelin oligodendrocyte glycoprotein 35-55 (MOG[35-55]), mice of the non-obese diabetic (NOD) genetic background develop a paralytic disease characterized by repeated relapses and remissions, which is followed by a chronic phase, a disease course that more closely reflects MS. We therefore exploited a MOG[35-55]-specific T cell receptor transgenic mouse strain on the NOD background, called 1C6, to determine whether adoptive transfer of myelin-specific CD4+ T cells to NOD background mice can invoke an RR-SP disease course. 1C6 CD4+ T cells were differentiated into Th1 or Th17 subsets that were adoptively transferred to NOD.Scid recipient mice, which we monitored for signs of EAE over the course of 100 days. Female Th1 recipients developed EAE with a day of onset (DOO) of 17 +/- 1.4 and a mean disease severity (MDS) of 2.2 +/- 0.2, while Th17 recipients developed EAE with DOO 10.5 +/- 1 and MDS 3 +/- 0.2. Both Th1 and Th17 recipients displayed leukocytic infiltration, demyelination and partial axonal preservation in the brainstem and spinal cord. However, recipients of female Th1 or Th17 cells never experienced a chronically worsening SP phase. By contrast, both male 1C6 Th1 recipients (DOO of 9.7 +/- 0.5, MDS of 3.4 +/- 0.1) and Th17 recipients (DOO of 7.3 +/- 0.6, MDS of 5.0 +/- 0) showed highly severe EAE. Male Th17 recipients displayed a RR-SP disease course that resulted in 100% mortality by d50. No significant differences in the frequency of IFN-gamma-positive or IL-17A-positive CNS-infiltrating CD4+ T cells were observed between males and females; intriguingly, male Th1 recipients displayed significantly fewer TNF-alpha-positive (p< 0.0001) CNS-infiltrating T cells, while male Th17 recipients showed significantly fewer GM-CSF-positive T cells (p< 0.05). These data demonstrate that male sex is an aggravating factor in an adoptive transfer model of EAE on the NOD strain, potentially via effects on innate immune cells or the CNS compartment.
Disclosure: Prenitha Mercy Ignatius Arokia Doss: nothing to disclose.
Asmita Yeola: nothing to disclose.
Joanie Baillargeon: nothing to disclose.
Hans Lassmann: nothing to disclose.
Ana Anderson: nothing to disclose.
Manu Rangachari: invited speaker, EMD Serono, Canada and Biogen Canada; preceptorship, Hoffmann-La Roche, Ltd; recipient of an unrestricted Transitional Career Development Award from EMD Serono, Canada and the endMS Network (2011-2016).