title: Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines.
abstract: T-cell clones generated from both CD4+CD25+ and CD8+CD25+ human thymocytes were assessed for their ability to suppress the proliferative response to allogeneic stimulation of type 1 T-helper (Th1) or type 2 T-helper (Th2) clones derived from autologous CD4+CD25- thymocytes. Both CD4+ and CD8+ T-regulatory (Treg) cells completely suppressed the proliferation of Th1 clones but exhibited significantly lower suppressive activity on the proliferation of Th2 clones. The partial suppressive effect on Th2 cells was further reduced by the addition in culture of interleukin-4 (IL-4), whereas it was increased in the presence of an anti-IL-4 monoclonal antibody (mAb). The suppressive activity on Th2 clones was also completely inhibited by the addition of IL-7, IL-9, and IL-15 but not of IL-2, whereas the suppressive effect on Th1 clones was only reverted by the addition of IL-15. Of note, Th2 clones expressed significantly higher amounts of mRNA for IL-4 receptor (IL-4R) and IL-9R alpha chains than Th1 clones, whereas the expression of mRNA for IL-2R, IL-7R, and IL-15R alpha chains was comparable. Taken together, these findings demonstrate that Th2 cells have a lower susceptibility than Th1 cells to the suppressive activity of human CD25+ regulatory thymocytes, because they are able to produce, and to respond to, growth factors distinct from IL-2, such as IL-4 and IL-9.
authors.affiliation: Department of Internal Medicine, University of Florence, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cosmi
authors.forename: Francesco
authors.initials: F
authors.lastname: Liotta
authors.forename: Roberta
authors.initials: R
authors.lastname: Angeli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzinghi
authors.forename: Veronica
authors.initials: V
authors.lastname: Santarlasci
authors.forename: Roberto
authors.initials: R
authors.lastname: Manetti
authors.forename: Laura
authors.initials: L
authors.lastname: Lasagni
authors.forename: Vittorio
authors.initials: V
authors.lastname: Vanini
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnani
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
authors.forename: Sergio
authors.initials: S
authors.lastname: Romagnani
mesh_terms: D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D007378:Interleukins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4