Open AccessImmunomodulation of human intestinal T cells by the synthetic CD80 antagonist RhuDex®
Author(s) -
Heninger AnneKristin,
Wentrup Sabine,
AlSaeedi Mohammed,
Schiessling Serin,
Giese Thomas,
Wartha Florian,
Meuer Stefan,
SchröderBraunstein Jutta
Publication year - 2014
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/iid3.34
Subject(s) - lamina propria , cd80 , cd86 , biology , inflammation , immunology , t cell , microbiology and biotechnology , cd28 , immune system , cd40 , cytotoxic t cell , in vitro , epithelium , biochemistry , genetics
Deregulated activation of mucosal lamina propria T cells plays a central role in the pathogenesis of intestinal inflammation. One of the means to attenuate T cell activation is by blocking the CD28/CD80 co‐stimulatory pathway. Here we investigate RhuDex®, a small molecule that binds to human CD80, for its effects on the activation of lamina propria T cells employing a gut‐culture model of inflammation. To this end, lamina propria leukocytes (LPL) and peripheral blood lymphocytes (PBL) were stimulated either through the CD3/T‐cell‐receptor complex or the CD2‐receptor (CD2) employing agonistic monoclonal antibodies. Co‐stimulatory signals were provided by CD80/CD86 present on lamina propria myeloid cells or LPS‐activated peripheral blood monocytes. Results show that RhuDex® caused a profound reduction of LPL and PBL proliferation, while Abatacept (CTLA‐4‐Ig) inhibited LPL proliferation to a small degree, and had no effect on PBL proliferation. Furthermore, Abatacept significantly inhibited IL‐2, TNF‐α, and IFN‐γ release from LPL, primarily produced by CD4 + T cells, where IL‐2 blockage was surprisingly strong, suggesting a down‐regulating effect on regulatory T cells. In contrast, in the presence of RhuDex®, secretion of IL‐17, again mostly by CD4 + T cells, and IFN‐γ was inhibited in LPL and PBL, yet IL‐2 remained unaffected. Thus, RhuDex® efficiently inhibited lamina propria and peripheral blood T‐cell activation in this pre‐clinical study making it a promising drug candidate for the treatment of intestinal inflammation.