Natural killer receptors distribution in multiple sclerosis: Relation to clinical course and interferon-beta therapy.
NK cell receptors (NKR) are expressed in subsets of NK and CD8+ T cells, lymphocytes involved in multiple sclerosis (MS) pathogenesis. Clinical implications of NKR expression in MS are unknown. Here, we show that the proportions of CD8+ T cells displaying LILRB1, an inhibitory NKR expressed at late stages of T cell differentiation, were directly related with age and MS duration, and inversely with the immunomodulatory therapy-dependent increase of CD56(bright) NK cells. Similar associations were found for KIR+ and CD56+ CD8+ T cells, whereas no age-related NKR distribution was perceived in controls. Moreover, active MS had lower LILRB1+ NK cells, and IFN-β-treated patients exhibited a phenotypic profile related to shorter disease evolution. Progressive accumulation of terminally differentiated T lymphocytes and experienced NK cells in MS, presumably stimulated in response to a persistent challenge and modulated by IFN-β therapy, may support the analysis of NKR distribution as new biomarkers.
Martínez-Rodríguez
J E
JE
Neurology Department, Hospital del Mar, Barcelona, Spain. 95917@parcdesalutmar.cat
Saez-Borderías
A
A
Munteis
E
E
Romo
N
N
Roquer
J
J
López-Botet
M
M
D000328:Adult; D000375:Aging / Q000378:metabolism; D000906:Antibodies / Q000097:blood / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D054340:Receptors, KIR / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000378:metabolism*; D012008:Recurrence; D013997:Time Factors
D000906:Antibodies; D015703:Antigens, CD; D015415:Biomarkers; D019002:CD56 Antigen; C527054:KLRC1 protein, human; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D055654:NK Cell Lectin-Like Receptor Subfamily C; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell; D016899:Interferon-beta