Relapses in multiple sclerosis are associated with increased CD8+ T-cell mediated cytotoxicity in CSF.
MS is thought to be mediated by CD4(+) T-helper cells. To investigate the importance of CD8(+) cytotoxic T-cells in MS we analyzed peripheral blood T-cells by DNA microarray, and plasma and CSF levels of granzymes from MS patients and controls. Cytotoxic gene expression was decreased in peripheral T-cells from RRMS patients whereas plasma levels of granzymes were unchanged. However, granzyme levels were elevated in the CSF of RRMS patients at relapse compared with controls and remission. Thus, CD8+ T-cell-mediated cytotoxicity is confined to the CSF/CNS compartment in RRMS patients and may be involved in the immunopathogenesis of clinical relapses.
Malmeström
Clas
C
Sahlgrenska Academy, Department of Neurology, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
Lycke
Jan
J
Haghighi
Sara
S
Andersen
Oluf
O
Carlsson
Lena
L
Wadenvik
Hans
H
Olsson
Bob
B
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D020789:Cathepsin C / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology; D053804:Granzymes / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; C075005:GNLY protein, human; D012333:RNA, Messenger; D054353:Perforin; D020789:Cathepsin C; D053804:Granzymes