title: Interference of the CD30-CD30L pathway reduces atherosclerosis development.
abstract: OBJECTIVE
  Costimulatory molecules tightly control immune responses by providing positive signals that promote T-cell activation or by transducing inhibitory signals that limit T-cell responses. CD30 and CD30L are members of the tumor necrosis factor receptor superfamily and are involved in the activation and proliferation of T and B cells, which have been implicated in the initiation and progression of atherosclerosis. In the present study, we thus aimed to determine the role of the CD30-CD30L pathway in the development of atherosclerosis.
  
  
  RESULTS
  Western-type diet-fed low-density lipoprotein receptor-deficient mice were treated with an anti-CD30L antibody for 8 weeks, which resulted in a reduction of atherosclerotic lesion formation in the aortic root by 35%. Reduced numbers of adventitial CD3(+) T cells were found in anti-CD30L-treated mice, whereas no differences were observed in collagen and macrophage content of the atherosclerotic lesions. B-cell and mast cell responses were also not affected on anti-CD30L treatment. Interestingly, splenocyte proliferation was reduced by 53%, whereas T-cell numbers were concomitantly reduced in anti-CD30L-treated mice compared with control mice. These data thus indicate that the CD30-CD30L pathway solely exerts its function via inhibition of T-cell responses.
  
  
  CONCLUSIONS
  In the present study, we are the first to show that interruption of the CD30-CD30L pathway reduced initial atherosclerosis development by modulating T-cell function.
authors.affiliation: Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands. a.c.foks@lacdr.leidenuniv.nl
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Foks
authors.forename: Ilze
authors.initials: I
authors.lastname: Bot
authors.forename: Vanessa
authors.initials: V
authors.lastname: Frodermann
authors.forename: Saskia C A
authors.initials: SC
authors.lastname: de Jager
authors.forename: Mariette
authors.initials: M
authors.lastname: Ter Borg
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van Santbrink
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
authors.forename: Gijs H M
authors.initials: GH
authors.lastname: van Puijvelde
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D053285:CD30 Ligand / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D017730:Ki-1 Antigen / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000473:pathology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D053285:CD30 Ligand; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D017730:Ki-1 Antigen; D011973:Receptors, LDL