Isolation and characterization of CD8+ regulatory T cells in multiple sclerosis.
To investigate CD8+ regulatory T cell influence on multiple sclerosis development, peripheral blood and cerebrospinal fluid (CSF) CD8+ T cell clones (TCCs) recognizing MBP(83-102) and MOG(63-87)-specific CD4+ T cells were isolated from 20 patients during acute exacerbations, 15 in remission and 15 controls. Blood and CSF CD8+ regulatory TCC cloning frequency decreased more during exacerbations than remissions or controls. Target cell pre-activation significantly enhanced CD8+ T granule-mediated cell killing of CD4+ targets, and was restricted by HLA-E. During exacerbations, killer-inhibitory receptor CD94/NKG2A expression was significantly higher in CD8+ TCCs, limiting their cytotoxic activity. Moreover, IL-15 and IFN-gamma significantly increased CD94 and NKG2A expression. These data provide evidence that CD94/NKG2A receptors play an important role in regulating T cell activity during the course of MS.
Correale
Jorge
J
Department of Neurology, Raúl Carrea Institute for Neurological Research, FLENI, Montañeses 2325, (1428) Buenos Aires, Argentina. jcorreale@fleni.org.ar
Villa
Andrés
A
D000328:Adult; D018106:CD28 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D004676:Myelin Basic Protein / Q000494:pharmacology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D054353:Perforin / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D018106:CD28 Antigens; D016207:Cytokines; C527054:KLRC1 protein, human; D004676:Myelin Basic Protein; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D054353:Perforin; D053804:Granzymes