The CD40/CD40L dyad, an immune checkpoint regulator, plays a protective role against Mouse hepatitis virus-induced neuroinflammatory demyelination

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B155
Abstract ID: 4389

Presenting Author:
Jayasri Das Sarma , Professor at Indian Inst. of Sci. Edu. and Res., Kolkata, Penn Med.

Abstract:

Murine ꞵ-coronavirus, RSA59, infection results in meningoencephalitis, demyelination, and axonal loss. CD40-CD40L dyad serves as an important immune checkpoint regulator during this disease pathobiology. C57BL/6 WT, CD4^-/-, CD40L^-/- and CD40^-/- mice were intracranially inoculated with RSA59 to study the acute phase neuroinflammation and chronic phase demyelination.  Studies suggested that CD4⁺ T cells play a protective role against RSA59-induced demyelination because, in the absence of CD4 gene, mice were more susceptible to acute poliomyelitis and chronic demyelination with axonal bulbar vacuolation. CD40L expressed by CD4⁺ T cells is crucial for host immunity against RSA59. Without CD40L in activated CD4⁺ T cells, RSA59-infected mice experience increased disease severity, dampened microglia/macrophage activation, reduced T cell infiltration in the CNS, and impaired T cell priming in the cervical lymph node. In the chronic phase, extensive CNS virus replication leads to severe demyelination and axonopathy due to altered microglia/macrophage populations caused by the absence of the CD40L gene. CD40-deficiency revealed increased acute phase encephalitis in the RSA59-infected groups due to increased infiltrating neutrophils, leading to heightened bystander neuroinflammation. Hence, it is evident that the RSA59-induced demyelination model elucidates an extensively robust innate immune system upon which adaptive immunity is built during the chronic stage of infection.