Open AccessAgonistic anti‐CD40 promotes early development and increases the incidence of severe thyroid epithelial cell hyperplasia (TEC H/P) in CD4−/− mice
Author(s) -
Yu Shiguang,
Downey Edward F.,
BraleyMullen Helen
Publication year - 2013
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.5
Subject(s) - tec , cd8 , cd40 , adoptive cell transfer , hyperplasia , medicine , endocrinology , chemistry , cancer research , immunology , t cell , cytotoxic t cell , immune system , biochemistry , astronomy , in vitro , ionosphere , physics
IFN‐γ−/−NOD.H‐2h4 mice develop thyroid epithelial cell hyperplasia (TEC H/P) characterised by abnormal proliferation of thyrocytes and infiltration of thyroids by CD4+ and CD8+ T cells, macrophages and dendritic cells. CD8+ T cells from mice with severe TEC H/P transfer similar lesions to SCID recipients, whereas CD4+ T cells transfer mild TEC H/P. CD4− and CD8− deficient IFN‐γ−/−NOD.H‐2h4 mice were generated to determine if CD4+ T cells were required for initial activation of the CD8+ T cells that transfer TEC H/P. After 6–8 months on NaI water, only 2 of 60 CD8−/− mice developed severe TEC H/P, whereas 31 of 101 CD4−/− mice developed severe TEC H/P and fibrosis comparable in severity to that of IFN‐γ−/− mice. However, splenocytes from CD4−/− mice with severe TEC H/P did not effectively transfer severe TEC H/P to SCID recipients. When CD4−/− donors were given agonistic anti‐CD40 mAb, most developed severe TEC H/P and their cells transferred severe TEC H/P to SCID recipients. These results indicate that agonistic anti‐CD40 can provide an important signal for activation of autoreactive CD8+ T cells that transfer severe TEC H/P. Therefore, targeting or blocking CD40 could provide effective therapy for diseases involving hyperplasia and fibrosis mediated by CD8+ T cells.