CD30 antigen: not a physiological marker for TH2 cells but animportant costimulator molecule in the regulation of the balance between TH1/TH2 response (Articolo in rivista)

Type
Label
  • CD30 antigen: not a physiological marker for TH2 cells but animportant costimulator molecule in the regulation of the balance between TH1/TH2 response (Articolo in rivista) (literal)
Anno
  • 2003-01-01T00:00:00+01:00 (literal)
Alternative label
  • Pellegrini P; Berghella AM; Contatsta I; Adorno D. (2003)
    CD30 antigen: not a physiological marker for TH2 cells but animportant costimulator molecule in the regulation of the balance between TH1/TH2 response
    in Transplant immunology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Pellegrini P; Berghella AM; Contatsta I; Adorno D. (literal)
Pagina inizio
  • 49 (literal)
Pagina fine
  • 61 (literal)
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  • 4 types of whole blood culture were used: 1° stimulated with anti-CD3 mAb which generates a CD30 cytokine profile similar to alloreactive stimulation; 2°with anti-CD3 mAb +M81 to inhibit CD30/CD30L interaction; 3°with anti-CD3 +anti-IL4 mAbs to counteract IL4 activity and 4° with anti-CD3+anti-IFNg mAbs to counteract IFNg activity. Network interactions between sCD30, sBcl2 and TH1/TH2 cytokines were then studied.The CD30-stimulated network, in fact, induces IFNg production linked to TH1 activity which is subsequently integrated by IL4 production linked to TH2 activity . This production appears regulated respectively by IL12p40 and IL12p70 production which maintain the balance between TH1/TH2 type response.The immunoregulatory activity of CD30 was confirmed by the lack of production balance between the above cytokines observed in cultures in which the interaction between CD30 and its natural ligand and IL4 or IFNg activity had been blocked. (literal)
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  • 12 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • Nuovi meccanismi fisiologici immunoregolatori per l'equilibrio TH1/TH2 , risposta e tolleranza immunitaria (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Understanding the physiological role of CD30 would be an important step forward in transplants because CD30+ T cells can be induced by alloantigens even in the presence of immunosuppressives such as cyclosporine and hence can act as regulatory cells in allograft.The results of functional studies on purified T CD30+ cell populations lead us to hypothesize that the CD30 costimulator molecule is not a specific marker for TH2 cells in normal conditions, as has been suggested, but rather a marker for an important immunoregulatory subpopulation that regulates the balance between TH1 and TH2 type response. To substantiate this hypothesis we studied the TH1/TH2 cytokine network in peripheral whole blood cultures stimulate with M44 CD30 ligand, an agonistic monoclonal antibody. Our results confirm the hypothesis above by showing that CD30 signals trigger functional mechanisms responsible for changes in levels of production of several important TH1 and TH2 cytokines involved in the regulation of the physiological balance between TH1/TH2 functions.We therefore conclude that CD30 may be an important costimulatory molecule and marker for the physiological balance between TH1/TH2 immune response. Consequently, further study of CD30 immunoregulatory mechanisms may allow for the identification of methods for re-establishing equilibrium and hence more effective strategies for the prevention and treatment of immunopathological conditions such as transplant rejection. (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto CNR per i Trapianti d'Organo e l'Immunocitologia (literal)
Titolo
  • CD30 antigen: not a physiological marker for TH2 cells but animportant costimulator molecule in the regulation of the balance between TH1/TH2 response (literal)
Abstract
  • Understanding the physiological role of CD30 would be an important step forward in transplants because CD30+ T cells can be induced by alloantigens even in the presence of immunosuppressives such as cyclosporine (Csa) and hence can act as regulatory cells in allograft. The results of functional studies on purified T CD30+ cell populations lead us to hypothesize that the CD30 costimulator molecule is not a specific marker for TH2 cells in normal conditions, as has been suggested, but rather a marker for an important immunoregulatory subpopulation that regulates the balance between TH1 and TH2 (TH1/TH2) type response. To substantiate this hypothesis we studied the TH1/TH2 cytokine network in peripheral whole blood cultures stimulate with M44 CD30 ligand (CD30L), an agonistic monoclonal antibody (mAb). Four types of whole blood culture were used: the first had been stimulated with anti-CD3 mAb which generates a CD30 cytokine profile similar to alloreactive stimulation; the second with anti-CD3 mAb + M81 (an anti-CD30L mAb) to inhibit CD30/CD30L interaction; the third with anti-CD3 + anti-interleukin (IL)4 mAbs to counteract IL4 activity and the fourth with anti-CD3+anti-interferon (IFN)g mAbs to counteract IFNg activity. Network interactions between soluble CD30 (sCD30, a maker of CD30 expression), sBcl2 (a marker of cell survival) and TH1/TH2 cytokines (IFNg, IL2, IL12p70, IL12p40, IL4, IL5 and IL10) were then studied in the supernatants obtained. Our results confirm the hypothesis above by showing that CD30 signals trigger functional mechanisms responsible for changes in levels of production of several important TH1 and TH2 cytokines involved in the regulation of the physiological balance between TH1/TH2 functions. The CD30-stimulated network, in fact, induces IFNg production linked to TH1 activity (®TH1) which is subsequently integrated by IL4 production linked to TH2 activity (®TH2). This production appears to be regulated respectively by IL12p40 (®TH2) and IL12p70 (®TH1) production which could maintain the balance between TH1/TH2 type response (TH1«TH2). Further CD30 mechanisms are the regulation of the interactions between: IL5-IFNg, IL5-IL4, IL2-IL10, IL2-IL12p40 and IL10-IL12p70 production. The immunoregulatory activity of CD30 was confirmed by the lack of production balance between the above mentioned cytokines observed in cultures in which the interaction between CD30 and its natural ligand (CD30/CD30L) and IL4 or IFNg activity had been blocked. We therefore conclude that CD30 may be an important costimulatory molecule and marker for the physiological balance between TH1/TH2 immune response. Consequently, further study of CD30 immunoregulatory mechanisms may allow for the identification of methods for re-establishing equilibrium and hence more effective strategies for the prevention and treatment of immunopathological conditions such as transplant rejection. (literal)
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