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Interleukin‐6 signalling mediates Galectin‐8 co‐stimulatory activity of antigen‐specific CD 4 T‐cell response
Author(s) -
Carabelli Julieta,
Prato Cecilia A.,
Sanmarco Liliana M.,
Aoki Maria P.,
Campetella Oscar,
Tribulatti María V.
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12980
Subject(s) - antigen , immune system , biology , ovalbumin , microbiology and biotechnology , t cell , co stimulation , cytokine , antigen presenting cell , cd40 , interleukin 2 , chemistry , cytotoxic t cell , immunology , cd28 , biochemistry , in vitro
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 CD 4 T cells. With this aim, splenocytes from DO 11.10 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 CD 4 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.