ABSTRACT
CD134/OX40, a member of the tumor necrosis factor receptor superfamily, is a cell-specific receptor for human herpesvirus 6 (HHV-6) variant B. Patients with drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) present a significant increase in CD134 expression in peripheral blood CD4+ T cells. We aimed to investigate the frequency of CD134+ CD4 T cells infiltrating skin lesions in patients with DIHS/DRESS and its association with disease severity. We retrospectively included 21 patients with DIHS/DRESS and 11 patients with erythema multiforme (EM). By immunohistochemistry, the frequency of CD134+ CD4 T cells in DIHS was significantly higher than that in EM (p = 0.0083). The DIHS/DRESS severity score was significantly correlated with the frequency of CD134+ CD4 T cells (p = 0.0272); moreover, there was a significant difference between severe and mild/moderate cases. Double immunofluorescence staining revealed that numerous cells presented CD134/CD4 and CD134/Foxp3 overlap in patients with DIHS/DRESS. These data suggest increased susceptibility to HHV-6 infection at localized skin sites. HHV-6 may be involved in the mechanism underlying the progression and pathophysiology of DIHS/DRESS.
Subject(s)
Drug Hypersensitivity Syndrome , Eosinophilia , Herpesvirus 6, Human , Humans , Retrospective Studies , Eosinophilia/pathology , Skin/pathologyABSTRACT
Objective:To investigate the effect of anti-CD134 mAb or CTLA4Ig on ConA induced splenic cell proliferation,Th cytokine secretion and production of anti-dsDNA antibody from splenic lymphtocyte in vitro in lupus-prone BXSB mice. Methods:Eighteen male lupus-prone BXSB mice model and 6 syngeneic normal C57BL/6 male mice were used in the experiment. The model mice were divided into three groups:un-treated group,Lupus recipe(LR) treated group and prednisone(pred. ) treated group. The mice's splenic cell suspension from above groups was culture stimulated by ConA respectively. The splenic cells from un-treated model mice were further divided into Anti-GD134L mAb,CTLA4Ig or Anti-CD134L mAb + CTLA4Ig treated subgroups. The ConA induced splenic cell proliferation was measured by MTT colorimetric assay. The levels of IFN-?, IL-6 and anti-dsDNA antibody in cell supernatant were measured by ELISA. Results; (1 )The splenic cell proliferative reaction and contents of IFN-?,IL-6 and anti-dsDNA antibody in cell supernatant of either spontaneous or ConA induced culture in the un-treated model group were obviously higher than that of the normal control or other groups. (2) The splenic cell proliferative reaction and production of IFN-?,IL-6 and anti-dsDNA antibody in the CD134L/CTLA4Ig treated group,LR treated goup or pred. treated group was not different from the normal control significantly. (3)To compared with CD134L treated group or CTLA4Ig treated gruop,the CD134L/CTLA4Ig and prednisone reduced significantly the splenic cell proliferative reaction and production of IFN-?,IL-6 and anti-dsDNA antibody in cell supernatant of either spontaneous or ConA induced culture,while no difference was found between CD134L treated group and CTLA4Ig treated proup. Conclusion:The lupus-prone BXSB mice might present abnormal lymphocyte proliferation,spontaneously express cytokines and secrete high level of autoantibody during the SLE development. LR and corticosteroids could obviously inhibit the abnormal lymphocyte proliferation;reduce the Th cytokine formation and antoantibody production Blockade of CD134-CD134L or B7-CD28 costimulatory pathway by Anti-CD134L rnAb or CT-LA4Ig could inhibit the activation of T cells and B cells like LR and corticosteroids. Furthermore, by blockade of both CD134-CD134L and CD28-B7 pathways,the frequency of alloreactive T cell was markedly reduced and was maintained at low levels so as to treat SLE effectively.
