title: Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts.
abstract: BACKGROUND
  Cystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease resistance, whereas Th2 cytokines are related to disease susceptibility and chronicity. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures.
  
  
  RESULTS
  We enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the "active stages" group compared to the "inactive stages" group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE.
  
  
  CONCLUSIONS
  We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence.
authors.affiliation: Translational Research Unit Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Petrone
authors.affiliation: Translational Research Unit Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vanini
authors.affiliation: Translational Research Unit Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Petruccioli
authors.affiliation: Unit of Surgery and Transplantation "Interaziendale" Department, P.O.I.T., Polo Ospedaliero Interaziendale San Camillo-INMI Lazzaro Spallanzani, Rome, Italy.
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Ettorre
authors.affiliation: Department of Radiology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Schininà
authors.affiliation: Department of Radiology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), IRCCS, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Busi Rizzi
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità (ISS), IRCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ludovisi
authors.affiliation: Clinical Department, National Institute for Infectious Diseases (INMI), IRCCS, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Corpolongo
authors.affiliation: Scientific Direction, National Institute for Infectious Diseases (INMI), IRCCS, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.affiliation: Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità (ISS), IRCCS, Rome, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pozio
authors.affiliation: Department of Infectious and Tropical Diseases, Sant'Andrea Hospital, "Sapienza" University, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Teggi
authors.affiliation: Translational Research Unit Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004443:Echinococcosis / Q000276:immunology*; D048209:Echinococcus granulosus / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016207:Cytokines