MHC class II antigen expression and T-cell infiltration in the demyelinating CNS and PNS of the twitcher mouse.
The expression of the major histocompatibility complex class II antigens (Ia) was investigated in the central and peripheral nervous systems of the twitcher mouse, an authentic murine model of globoid cell leukodystrophy (Krabbe disease) in humans. In this mutant, demyelination is noted as early as postnatal day 10 in the peripheral nerve and day 20 in the spinal cord. Emergence of Ia antigen expressing cells (Ia+ cells) was largely coincident with the initiation of demyelination, suggesting the importance of local factors for the induction of Ia antigens. Ia+ cells gradually increased in number with the progression of demyelination, but reached a plateau between postnatal days 30 and 40, then rapidly decreased despite continuous demyelination in both central and peripheral nervous systems. The only exception was in the spinal cord where Ia+ cells were numerous even at postnatal day 50. The cells expressing L3T4 antigen (L3T4+ cells), which is a mouse CD4 antigen, and the interleukin-2 receptor antigen expressing cells (IL-2R+ cells), also appeared in the regions where Ia+ cells were observed. L3T4+ cells were still abundant after P45, when Ia+ and IL-2R+ cells decreased. Combined autoradiographic and immunocytochemical studies demonstrated mitotic activity in a few Ia+ cells. However, low labeling indices of Ia+ cells in both cerebrum and sciatic nerve suggest that the increase of Ia+ cells was largely due to either induction of Ia antigens on local cells or new recruitment of Ia+ cells from the circulation. Expression of Ia antigens associated with an emergence of L3T4+ or IL-2R+ cells in the demyelinating lesions may indicate involvement of immunological responses in the pathogenesis of this metabolic demyelinating disorder. Alternatively, these apparent immunological phenomena may be tentative and non-specific local reactions to degenerating tissue components such as myelin. The mechanism(s) regulating the expression of Ia antigens in this genetic metabolic demyelinating disease is yet to be determined.
Ohno
M
M
Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.
Komiyama
A
A
Martin
P M
PM
Suzuki
K
K
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D003711:Demyelinating Diseases / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008818:Mice, Neurologic Mutants; D017933:Peripheral Nervous System / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D014316:Tritium; D013936:Thymidine