Lymphocytes utilise sialylated surface molecules to accumulate in developing lesions of autoimmune encephalomyelitis.
The accumulation of desialylated radiolabelled normal spleen cells and non-neuroantigen specific CD4 T-lymphocytes was measured in the lumbosacral spinal cord of Lewis rats with autoimmune encephalomyelitis (EAE) induced with myelin basic protein in Freund's adjuvant. The labelled cells were preincubated with sialidase and thoroughly washed prior to intravenous injection into rats exhibiting early clinical signs of EAE. Four hours later, the rats were killed and blood and spinal cord samples were radioassayed. Compared with untreated cells, desialylation markedly reduced the accumulation of both normal spleen cells and memory T-lymphocytes in the spinal cord, despite similar levels of cells being present in the blood. In another experiment, the accumulation of desialylated, macrophage-depleted spleen lymphocytes was measured during the onset, recovery and short-term "relapse" phases of acute EAE. Again, compared with controls the accumulation of desialylated lymphocytes was always significantly less, despite similar numbers of cells in the circulation. Lastly, intravenous injections of sialidase produced delayed onset of both clinical and histological signs in rats with passively-transferred EAE. These data confirm and extend previous findings, using a different animal model, that sialyl residues on the lymphocyte surface are important to the accumulation of such cells at inflammatory sites in the central nervous system. The possible relevance of these findings to human demyelinating disease is discussed.
Simmons
R D
RD
Neurosciences Research Unit, Woden Valley Hospital, Canberra, Australia.
Cattle
B A
BA
Hugh
A R
AR
Willenborg
D O
DO
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019040:E-Selectin; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007116:Immunization, Passive; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009439:Neuraminidase / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D012794:Sialic Acids / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D012794:Sialic Acids; D009439:Neuraminidase