Differential T cell response in central and peripheral nerve injury: connection with immune privilege.
The central nervous system (CNS), unlike the peripheral nervous system (PNS), is an immune-privileged site in which local immune responses are restricted. Whereas immune privilege in the intact CNS has been studied intensively, little is known about its effects after trauma. In this study, we examined the influence of CNS immune privilege on T cell response to central nerve injury. Immunocytochemistry revealed a significantly greater accumulation of endogenous T cells in the injured rat sciatic nerve than in the injured rat optic nerve (representing PNS and CNS white matter trauma, respectively). Use of the in situ terminal deoxytransferase-catalyzed DNA nick end labeling (TUNEL) procedure revealed extensive death of accumulating T cells in injured CNS nerves as well as in CNS nerves of rats with acute experimental autoimmune encephalomyelitis, but not in injured PNS nerves. Although Fas ligand (FasL) protein was expressed in white matter tissue of both systems, it was more pronounced in the CNS. Expression of major histocompatibility complex (MHC) class II antigens was found to be constitutive in the PNS, but in the CNS was induced only after injury. Our findings suggest that the T cell response to central nerve injury is restricted by the reduced expression of MHC class II antigens, the pronounced FasL expression, and the elimination of infiltrating lymphocytes through cell death.
Moalem
G
G
Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel Department of Immunology, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Monsonego
A
A
Shani
Y
Y
Cohen
I R
IR
Schwartz
M
M
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002493:Central Nervous System Diseases / Q000276:immunology / Q000473:pathology*; D017931:DNA Primers; D053222:Fas Ligand Protein; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000235:genetics; D009900:Optic Nerve / Q000378:metabolism; D020221:Optic Nerve Injuries; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D017931:DNA Primers; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D012333:RNA, Messenger