Enhanced microglial clearance of myelin debris in T cell-infiltrated central nervous system.
Acute multiple sclerosis lesions are characterized by accumulation of T cells and macrophages, destruction of myelin and oligodendrocytes, and axonal damage. There is, however, limited information on neuroimmune interactions distal to sites of axonal damage in the T cell-infiltrated central nervous system. We investigated T-cell infiltration, myelin clearance, microglial activation, and phagocytic activity distal to sites of axonal transection through analysis of the perforant pathway deafferented dentate gyrus in SJL mice that had received T cells specific for myelin basic protein (TMBP) or ovalbumin (TOVA). The axonal lesion of TMBP-recipient mice resulted in lesion-specific recruitment of large numbers of T cells in contrast to very limited T-cell infiltration in TOVA-recipient and -naïve perforant pathway-deafferented mice. By double immunofluorescence and confocal microscopy, infiltration with TMBP but not TOVA enhanced the microglial response to axonal transection and microglial phagocytosis of myelin debris associated with the degenerating axons. Because myelin antigen-specific immune responses may provoke protective immunity, increased phagocytosis of myelin debris might enhance regeneration after a neural antigen-specific T cell-mediated immune response in multiple sclerosis.
Nielsen
Helle Hvilsted
HH
Medical Biotechnology Center, University of Southern Denmark, Winsløwparken 25, DK-5000 Odense C, Denmark. hhnielsen@health.sku.dk
Ladeby
Rune
R
Fenger
Christina
C
Toft-Hansen
Henrik
H
Babcock
Alicia A
AA
Owens
Trevor
T
Finsen
Bente
B
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001369:Axons / Q000473:pathology*; D019771:Axotomy / Q000379:methods; D002452:Cell Count / Q000379:methods; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000502:physiology*; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism*; D009410:Nerve Degeneration / Q000276:immunology* / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D019580:Perforant Pathway / Q000293:injuries / Q000473:pathology; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D016177:Macrophage-1 Antigen; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins