title: CD4+T-bet+, CD4+pSTAT3+ and CD8+T-bet+ T cells accumulate in peripheral blood during NZB treatment.
abstract: Circulating T cells and monocytes expressing T-bet, pSTAT1 and pSTAT3 increase in relapsing-remitting multiple sclerosis (RRMS) during relapse. Natalizumab (NZB) is an effective drug in RRMS, but exacerbation of the disease after its discontinuation has been described in some patients. The aim of this research was to study the effect of NZB treatment on circulating lymphomonocyte subpopulations expressing T-bet, pSTAT1, pSTAT3 and CD4+CD25+Foxp3+ regulatory T cells. Flow cytometry was used to evaluate the percentages of circulating CD4+ and CD8+ T cells, CD14+ monocytes and B cells expressing T-bet, pSTAT1, and pSTAT3, and CD4+CD25+Foxp3+ regulatory T cells from RRMS patients before and after 6-12 NZB infusions. In NZB-treated RRMS patients, the percentages of CD4+pSTAT1+ and CD8+pSTAT1+ T cells, CD14+pSTAT1+ monocytes, CD4+T-bet+, CD8+T-bet+ and CD4+pSTAT3+ T cells and CD14+pSTAT3+ monocytes increased after 12 drug infusions and were similar to those observed in untreated relapsing RRMS patients. Otherwise in vitro NZB exposure of peripheral blood mononuclear cells from untreated RRMS patients and controls had no effect. It was concluded that NZB treatment determines an accumulation of CD4+pSTAT1+, CD8+pSTAT1+, CD4+T-bet+, CD8+T-bet+ and CD4+STAT3+ T cells in peripheral blood that may account for the exacerbation of the disease observed in some patients after the discontinuation of the drug.
authors.affiliation: Institute of Neurology, Department of Neurosciences, Catholic University, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Frisullo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Iorio
authors.forename: Domenico
authors.initials: D
authors.lastname: Plantone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marti
authors.forename: Viviana
authors.initials: V
authors.lastname: Nociti
authors.forename: Agata Katia
authors.initials: AK
authors.lastname: Patanella
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Batocchi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D007558:Italy; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab; D010766:Phosphorylation; D012008:Recurrence; D050794:STAT1 Transcription Factor / Q000097:blood; D050796:STAT3 Transcription Factor / Q000097:blood*; D020825:T-Box Domain Proteins / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult; D000098815:T-bet Transcription Factor
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007155:Immunologic Factors; D053645:Interleukin-2 Receptor alpha Subunit; D000069442:Natalizumab; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor