Abstracts (complete list) - Wissenschaft Online

Tea Gogishvili, Beate Geyer, Susanne Grunewald, Thomas Hünig
Blockade of CD28-mediated co-stimulation ameliorates
allergic airway inflammation in mice
Allergic airway inflammation is characterized by a Th2-mediated immune response and
cytokines, such as IL-4, IL-5 and IL-13 are predominantly responsible for eliciting the
pathogenic changes. Activation of naïve T-cells involves not only engagement of the
TCR by antigen, but also requires signals delivered through co-stimulation. Recent
studies have demonstrated the central role of CD28 in the induction of allergic airway
inflammation and immunotherapeutic options selectively targeting CD28 have been
suggested to be desirable. To investigate the requirement for CD28 for functional
activity of T-cells we examined the effects of an aCD28 mAb, which interferes with
CD28-B7 interaction, in a murine model of allergic airway inflammation. Treatment with
mAb was started before or after the allergic state had been established. Blockade of costimulation
by aCD28 mAb moderately reduced the number of CD4+ T cells. This effect
was associated with the reduced production of Th2 cytokines to the side of
inflammation. Interestingly, treatment with aCD28 did not influence IL-10 and IFNgamma
secretion. Examination of the airways demonstrated that OVA/Alum
sensitization led to infiltration of eosinophils, which was significantly reduced after
administration of aCD28. Moreover, total IgE was only slightly reduced, whereas
synthesis of OVA-specific IgE was significantly inhibited in treated groups. Thus, our
data demonstrate that blockade of co-stimulation with aCD28 mAb reduces Ag-driven
immune response in a murine model of allergic airway inflammation.