title: Dual role of anti-TNF therapy: enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues.
abstract: The impact of anti-TNF therapy on systemic immune responses in patients has not been clearly defined. Here, we examined Th1/Th2/Th17 cytokine expression, activation and proliferation of peripheral T cells from patients with psoriasis and inflammatory bowel disease before and during anti-TNF therapy. In parallel, we calculated the correlation with the clinical response and we monitored cytokine expression in biopsies from inflamed tissues. We evidenced a dual role of TNF-blockade. In peripheral blood, it increased the expression of cytokines such as IL-17, IL-10, and IFN-γ, and enhanced the expression of activation markers and the proliferative response of CD4 T cells to TCR stimulation. By contrast, in biopsies from target tissues, TNF-blockade diminished the expression of Th17/Th1 cytokine and early inflammatory genes. Importantly, the enhanced T cell responses to TCR-stimulation did not impair the clinical response to the therapy and, in responder patients, occurred with the concomitant down-regulation of inflammatory genes in the target tissues.
authors.affiliation: Department of Immunology, INGM-National Institute of Molecular Genetics, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bosè
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Raeli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garutti
authors.forename: Elena
authors.initials: E
authors.lastname: Frigerio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cozzi
authors.forename: Marco
authors.initials: M
authors.lastname: Crimi
authors.forename: Flavio
authors.initials: F
authors.lastname: Caprioli
authors.forename: Rossana
authors.initials: R
authors.lastname: Scavelli
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Altomare
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.forename: Eva
authors.initials: E
authors.lastname: Reali
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology; D001769:Blood / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology; D000068800:Etanercept; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000069285:Infliximab; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D014763:Viral Matrix Proteins; C030107:enterotoxin F, Staphylococcal; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept