Abstracts (complete list) - Wissenschaft Online

Oliver Frey, Lisa Bruns, Andreas Reichel, Lars Morawietz, Thomas Kamradt
Short-term depletion of regulatory T cells converts selflimiting
arthritis into a chronic disease
We have established a new arthritis model, induced by systemic immunization of nontransgenic
mice with the ubiquitous autoantigen glucose-6-phosphate isomerase. The
disease is dependent on B and T cells and is normally self limiting, leading to resolution
of inflammation between day 30-40 after disease induction. We hypothesized that
naturally occurring regulatory T cell (Treg) might be important for the resolution of the
disease and therefore investigated their role.
Treg cells were depleted by intraperitoneal injection of an anti-CD25-antibody. Arthritis
was induced by immunization of mice with recombinant G6PI. The severity of the
disease was assessed clinically on 0-3 point score for each limb and by histology at the
end of the experiments. The degree of Treg-depletion (FoxP3 staining) and cytokine
production was assessed by flow cytometry.
Injection of anti-CD25 antibody on days –11 and –8 before immunization resulted in a
transient reduction of Treg, which returned to base-line levels on the clinical peak of the
disease (d 12-15 after disease induction). This transient depletion profoundly affected
the disease course, resulting in chronic-destructive arthritis over the whole follow-up
period (80 days) with active inflammation and joint destruction, as evidenced by
histological examination. This exacerbated arthritis was accompanied by increased
numbers of IL-17-producing T cells and T cell proliferation.
We conclude from our experiments that Treg do not actively participate in the resolution
of arthritis, since the disease is still chronifies, when Treg cell number are fully
normalized. Our data show that they act rather in early stages of disease development
by controlling the extent of T cell activation.