Abstracts (complete list) - Wissenschaft Online

Hyun-Dong Chang, Jun Dong, Andreas Thiel Thiel, Andreas Radbruch
IL-10 Expression in Th lymphocytes is conditional
T helper (Th) lymphocytes have the ability to memorize the expression of cytokines
which they were instructed to express during the primary activation. Cytokine memory
can thus contribute to the maintenance of chronic inflammation. Cytokine memory is
accompanied by the stable upregulation of transcription factors and epigenetic
imprinting of cytokine genes. Here we analyse the memory of Th lymphocytes for the
reexpression of interleukin-10 (IL-10), critical in the regulation of immune responses
and reduction of immunopathology. IL-10 is induced by IL-4 and IL-12 and remains
conditional on the provision of the inducing cytokines. In addition, IL-10 expressing Th
cells isolated ex vivo using the cytometric cytokine secretion assay do not memorize IL-
10 expression upon repeated in vitro restimulations. Whereas repeated stimulation with
IL-4 leads to the establishment of a stable IL-10 memory which goes along with GATA-3
mediated epigenetic imprinting of the il10 gene, IL-12 induced IL-10 expression in Th1
cells requires continued IL-12 signaling. In accordance, we could detect no epigenetic
modifications in the il10 gene in ex vivo isolated and Th1 derived IL-10 expressing cells.
The maintained dependency of IL-10 expression of Th1 lymphocytes suggests an
unexpected anti-inflammatory potential of IL-12: In memory Th1 cells IL-10 expression
remains dependent on IL-12, while reexpression of IFN-γ is independent of the original
inducer IL-12. The exclusion of IL-10 from the functional memory of Th1 cells may
reflect the requirement for conditional regulation of inflammatory immune responses.