Abstracts (complete list) - Wissenschaft Online

Florian Reißfelder, Jutta Schröder-Braunstein, Thomas Giese, Carolin Reiser, Stefan
C. Meuer, Bernd Sido
Differential inhibition of human intestinal lamina propria Tlymphocyte
activation versus peripheral blood T cells by the
gold-compound auranofin
The oxidoreductase Thioredoxin (TRX) potentiates cytokine production in and
proliferation of lymphocytes. Human intestinal lamina propria T-cells (LPT) constitutively
contain high amounts of TRX, produce large quantities of cytokines and proliferate
vigorously upon CD2 stimulation as compared to peripheral blood T-cells (PBT). To
become immunologically active, oxidized TRX needs to be reduced by TRX reductase.
We, therefore, aimed to inhibit the immune response of LPT in vitro through Auranofin
(AF), a potent inhibitor of TRX reductase.
Isolated LPT from fresh surgical specimens of normal colon mucosa and autologous PBT
were stimulated via CD2 using a combination of mitogenic mAb. AF (0,5•M) inhibited
proliferation of LPT to nearly background levels, whereas it was enhanced in PBT.
Correspondingly, the vigorous cytokine mRNA expression in LPT following CD2
stimulation (IL2, TNFα, TNFβ, IFNγ, GMCSF) was nearly completely abolished by AF in
contrast to PBT, in which it was enhanced twofold. The CD2 immune response of LPT
was paralleled by a high-level expression of the antioxidative fraction of TRX as
determined by redox Western-blot analysis. This fraction was partly oxidized in LPT in
the presence of AF, whereas it was further increased in PBT. The differential
immunomodulatory activity of AF in LPT versus PBT was not due to differences in TRX
reductase expression. However, Annexin V and Propidium Iodide staining revealed that
LPT are constitutively more sensitive to spontaneous apoptosis than PBT, which is
further enhanced by AF during CD2 stimulation. Inflammatory bowel disease (IBD) is
characterized by hyperreactivity of LPT along with resistence to apoptosis as compared
to LPT from normal gut. AF may, thus, represent an innovative immunomodulatory
strategy in the therapy of IBD.