부산대학교 도서관

Summary: Galectin‐8 (Gal‐8) is a mammalian lectin endowed with the ability to co‐stimulate antigen‐specific immune responses. We have previously demonstrated that bone‐marrow‐derived dendritic cells produce high levels of interleukin‐6 (IL‐6) in response to Gal‐8 stimulation. As IL‐6 is a pleiotropic cytokine that has a broad effect on cells of the immune system, we aimed to elucidate whether IL‐6 was involved in Gal‐8‐dependent co‐stimulatory signals during antigen recognition by specific CD4 T cells. With this aim, splenocytes from DO11.10 mice were incubated with a low dose of the cognate ovalbumin peptide in combination with Gal‐8. Interleukin‐6 was found significantly increased in cultures stimulated with Gal‐8 alone or Gal‐8 plus cognate peptide. Moreover, IL‐6 signalling was triggered during Gal‐8‐induced co‐stimulation, as determined by phosphorylation of signal transducer and activator of transcription 3. Interleukin‐6 blockade by neutralizing monoclonal antibody precluded Gal‐8 co‐stimulatory activity but did not affect the antigen‐specific T‐cell receptor activation. Different subsets of dendritic cells, as well as macrophages and B cells, were identified as the cellular source of IL‐6 during Gal‐8‐induced co‐stimulation. To confirm that IL‐6 mediated the Gal‐8 co‐stimulatory effect, antigen‐presenting cells from IL‐6‐deficient or wild‐type mice were co‐cultured with purified CD4 T cells from OTII mice in the presence of cognate peptide and Gal‐8. Notably, Gal‐8‐induced co‐stimulation, but not the antigen‐specific response, was significantly impaired in the presence of IL‐6‐deficient antigen‐presenting cells. In addition, exogenous IL‐6 fully restored Gal‐8‐induced co‐stimulation. Taken together, our results demonstrate that IL‐6 signalling mediates the Gal‐8 immune‐stimulatory effect. Galectin‐8 (Gal‐8) has a predominant activating role in the elicitation of primary adaptive immune response by co‐stimulating borderline antigen‐specific T‐cell responses. In the present manuscript, we identified interleukin‐6 signalling as a key mediator of the co‐stimulation induced by Gal‐8 in the primary CD4 T‐cell response. We demonstrated that Gal‐8 induces antigen‐presenting cells to produce interleukin‐6, which synergizes T‐cell receptor activation during antigen recognition by CD4 T cells. [ABSTRACT FROM AUTHOR]