dc.contributor.author | Verhagen, Claudia E. | |
dc.contributor.author | de Boer, Tjitske | |
dc.contributor.author | Smits, Hermelijn H. | |
dc.contributor.author | Verreck, Frank A.W. | |
dc.contributor.author | Wierenga, Eddy A. | |
dc.contributor.author | Kurimoto, M. | |
dc.contributor.author | Lammas, D. Anthony | |
dc.contributor.author | Kumararatne, Dinakanthe S. | |
dc.contributor.author | Sanal, Ozden | |
dc.contributor.author | Kroon, Frank P. | |
dc.contributor.author | van Dissel, Jaap T. | |
dc.contributor.author | Sinigaglia, Francesco | |
dc.contributor.author | Ottenhoff, Tom H.M. | |
dc.date.accessioned | 2019-12-10T10:50:49Z | |
dc.date.available | 2019-12-10T10:50:49Z | |
dc.date.issued | 2000 | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.uri | https://doi.org/ | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193232/ | |
dc.identifier.uri | http://hdl.handle.net/11655/14387 | |
dc.description.abstract | Genetic lack of interleukin 12 receptor β1 (IL-12Rβ1) surface expression predisposes to severe infections by poorly pathogenic mycobacteria or Salmonella and causes strongly decreased, but not completely abrogated, interferon (IFN)-γ production. To study IL-12Rβ1–independent residual IFN-γ production, we have generated mycobacterium–specific T cell clones (TCCs) from IL-12Rβ1–deficient individuals. All TCCs displayed a T helper type 1 phenotype and the majority responded to IL-12 by increased IFN-γ production and proliferative responses upon activation. This response to IL-12 could be further augmented by exogenous IL-18. IL-12Rβ2 was found to be normally expressed in the absence of IL-12Rβ1, and could be upregulated by IFN-α. Expression of IL-12Rβ2 alone, however, was insufficient to induce signal transducer and activator of transcription (Stat)4 activation in response to IL-12, whereas IFN-α/IFN-αR ligation resulted in Stat4 activation in both control and IL-12Rβ1–deficient cells. IL-12 failed to upregulate cell surface expression of IL-18R, integrin α6, and IL-12Rβ2 on IL-12Rβ1–deficient cells, whereas this was normal on control cells. IL-12–induced IFN-γ production in IL-12Rβ1–deficient T cells could be inhibited by the p38 mitogen-activated protein kinase (MAP) kinase inhibitor SB203580 and the MAP kinase kinase (MEK) 1/2 inhibitor U0126, suggesting involvement of MAP kinases in this alternative, Stat4-independent, IL-12 signaling pathway., Collectively, these results indicate that IL-12 acts as a partial agonist in the absence of IL-12Rβ1. Moreover, the results reveal the presence of a novel IL-12Rβ1/Stat4–independent pathway of IL-12 responsiveness in activated human T cells involving MAP kinases. This pathway is likely to play a role in the residual type 1 immunity in IL-12Rβ1 deficiency. | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.title | Residual Type 1 Immunity In Patients Genetically Deficient For Interleukin 12 Receptor Β1 (Il-12Rβ1):Evidence for an IL-12Rb1–independent Pathway of IL-12
Responsiveness in Human T Cells | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.relation.journal | The Journal of Experimental Medicine | |
dc.contributor.department | Çocuk Sağlığı ve Hastalıkları | |
dc.identifier.volume | 192 | |
dc.identifier.issue | 4 | |
dc.identifier.startpage | 517 | |
dc.identifier.endpage | 528 | |
dc.description.index | PubMed | |
dc.description.index | WoS | |
dc.description.index | Scopus | |