Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.
Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.
Schmitt
A B
AB
Department of Neurology, Aachen University Medical School, Germany. andreas.schmitt@rwth-aachen.de
Buss
A
A
Breuer
S
S
Brook
G A
GA
Pech
K
K
Martin
D
D
Schoenen
J
J
Noth
J
J
Love
S
S
Schröder
J M
JM
Kreutzberg
G W
GW
Nacimiento
W
W
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001921:Brain / Q000276:immunology; D002102:Cadaver; D002544:Cerebral Infarction / Q000276:immunology / Q000503:physiopathology; D004525:Efferent Pathways / Q000276:immunology* / Q000503:physiopathology; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D017628:Microglia / Q000502:physiology*; D008875:Middle Aged; D009410:Nerve Degeneration; D010487:Periaqueductal Gray / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D011712:Pyramidal Tracts / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D012016:Reference Values; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000503:physiopathology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000502:physiology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000949:Histocompatibility Antigens Class II; D017493:Leukocyte Common Antigens; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C524898:PLAUR protein, human