Response of the axon and barrier endothelium to experimental allergic neuritis induced by autoreactive T cell lines.
Experimental allergic neuritis was induced in Lewis rats by inoculation with autoreactive T cell lines sensitized to residue 57-81 of P2 myelin protein. Control rats received cells derived from immunization to complete Freund's adjuvant alone. Endoneurial fluid pressure (EFP) was measured in both sciatic nerves at 0, 3, 5, 7, 9, and 11 days post-inoculation (PI). The temporal evolution of inflammatory disease was studied by correlating EFP with a morphometric analysis of the nerve microenvironment and with electron microscopic observations. Both edema, as evidenced by increased endoneurial extracellular space, and inflammation paralleled the time course of the EFP increase, reaching peak values at 7 days PI and declining to near-normal values after 11 days. Wallerian degeneration was detectable at 7 days and increased 9 days after inoculation. Axonal damage appeared at the height of the inflammatory process, when edema and increased EFP were maximal. Evidence of demyelination was apparent by 7 days and persisted through 11 days. The onset of edema was associated with changes in venular endothelial cells which tended to lose their normal scaphoid appearance and assumed rhomboid configurations reminiscent of high endothelial venules. At that point, the barrier endothelium was visibly disrupted with the loss of tight junctions and separation of adjacent cells. Specific cell-cell interactions took place between endothelial cells and infiltrating leukocytes as they immigrated into the endoneurial compartment. There was evidence of altered perineurial permeability with fibrin deposition and leukocyte infiltration between the layers of the perineurial sheath.
Powell
H C
HC
Department of Pathology, Neuropathology, University of California, San Diego.
Myers
R R
RR
Mizisin
A P
AP
Olee
T
T
Brostoff
S W
SW
D000818:Animals; D001369:Axons / Q000502:physiology*; D001826:Body Fluids / Q000502:physiology; D002460:Cell Line; D004727:Endothelium / Q000502:physiology; D005260:Female; D008854:Microscopy, Electron; D009420:Nervous System / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D011312:Pressure; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology*