Dept. of Neurology-Neuroimmunology; Vall d'Hebron University Campus; Multiple Sclerosis Centre of Catalonia (Cemcat)

Author Of 1 Presentation

Pathogenesis – Immunology Poster Presentation

P0972 - Impact of age on the immune system and the central nervous system in experimental autoimmune encephalomyelitis (ID 1598)

Speakers
Presentation Number
P0972
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

The debut of multiple sclerosis (MS) at an older age associates with increased risk of presenting a primary progressive form, an earlier conversion to the secondary progressive form and a greater disability accumulation. These facts could be due to the impact of immunosenescence (ISC) in elderly MS patients.

Objectives

To study the impact of aging on clinical outcome, histopathology of the central nervous system (CNS) and peripheral immune system in experimental autoimmune encephalomyelitis (EAE).

Methods

8-week old and 40-week old C57BL/6JRccHsd female mice immunized with MOG35-55 were used. Histopathological and immunological studies were performed in non-immunized mice (basal) and in EAE mice 14 days post-immunization (dpi) and 28 dpi. Immunofluorescence staining was performed in spinal cords to evaluate T cell infiltration (CD3), demyelination (MBP), reactive astrogliosis (GFAP), reactive microglia (LEA) and axonal damage (SMI32). Immune cell subsets and intracellular cytokines were analyzed in splenocytes by flow cytometry. Polyclonal and MOG-specific capacity of proliferation were assessed in splenocytes. Differences between young and old mice in each EAE time point and along disease course were analyzed.

Results

Old mice (OM) showed a more severe EAE clinical outcome compared to young ones. Different patterns along EAE course were observed for inflammation, axonal damage and reactive microglia (increased at 28 dpi in OM) as well as for reactive astroglia (decreased at 14 dpi in OM) in the CNS. The adaptive immune cell subsets showed more age-related changes in OM, presenting a different pattern along EAE course: naïve CD8+ T cells (decreased basally and at 28 dpi), effector/effector memory CD4+PD1+ T cells (increased basally and at 14 dpi), regulatory CD39+ T cells (increased basally and at 14 dpi) and MHC-II+ B cells (increased basally and at 14 dpi). Regarding innate immune cells, immature NK cells increased and mature NK cells decreased along EAE course in OM, and NKT cells also presented a different pattern along EAE course (decreased basally and at 28 dpi in OM). Cytokine producing T cells were increased in OM. No differences were observed in splenocyte-proliferative capacity.

Conclusions

Aging has an impact on EAE outcome being more severe in old mice. Major changes take place in the CNS and in the adaptive immune cell subsets in the periphery. Altogether suggest that age modifies the immunopathogenic mechanisms of EAE.

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Presenter Of 1 Presentation

Pathogenesis – Immunology Poster Presentation

P0972 - Impact of age on the immune system and the central nervous system in experimental autoimmune encephalomyelitis (ID 1598)

Speakers
Presentation Number
P0972
Presentation Topic
Pathogenesis – Immunology

Abstract

Background

The debut of multiple sclerosis (MS) at an older age associates with increased risk of presenting a primary progressive form, an earlier conversion to the secondary progressive form and a greater disability accumulation. These facts could be due to the impact of immunosenescence (ISC) in elderly MS patients.

Objectives

To study the impact of aging on clinical outcome, histopathology of the central nervous system (CNS) and peripheral immune system in experimental autoimmune encephalomyelitis (EAE).

Methods

8-week old and 40-week old C57BL/6JRccHsd female mice immunized with MOG35-55 were used. Histopathological and immunological studies were performed in non-immunized mice (basal) and in EAE mice 14 days post-immunization (dpi) and 28 dpi. Immunofluorescence staining was performed in spinal cords to evaluate T cell infiltration (CD3), demyelination (MBP), reactive astrogliosis (GFAP), reactive microglia (LEA) and axonal damage (SMI32). Immune cell subsets and intracellular cytokines were analyzed in splenocytes by flow cytometry. Polyclonal and MOG-specific capacity of proliferation were assessed in splenocytes. Differences between young and old mice in each EAE time point and along disease course were analyzed.

Results

Old mice (OM) showed a more severe EAE clinical outcome compared to young ones. Different patterns along EAE course were observed for inflammation, axonal damage and reactive microglia (increased at 28 dpi in OM) as well as for reactive astroglia (decreased at 14 dpi in OM) in the CNS. The adaptive immune cell subsets showed more age-related changes in OM, presenting a different pattern along EAE course: naïve CD8+ T cells (decreased basally and at 28 dpi), effector/effector memory CD4+PD1+ T cells (increased basally and at 14 dpi), regulatory CD39+ T cells (increased basally and at 14 dpi) and MHC-II+ B cells (increased basally and at 14 dpi). Regarding innate immune cells, immature NK cells increased and mature NK cells decreased along EAE course in OM, and NKT cells also presented a different pattern along EAE course (decreased basally and at 28 dpi in OM). Cytokine producing T cells were increased in OM. No differences were observed in splenocyte-proliferative capacity.

Conclusions

Aging has an impact on EAE outcome being more severe in old mice. Major changes take place in the CNS and in the adaptive immune cell subsets in the periphery. Altogether suggest that age modifies the immunopathogenic mechanisms of EAE.

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