3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Cutting Edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right.

      The Journal of Immunology Author Choice

      Adoptive Transfer, Animals, Antibodies, administration & dosage, immunology, Antigens, CD28, drug effects, metabolism, Antigens, CD3, Cell Differentiation, Cytokines, Encephalomyelitis, Autoimmune, Experimental, Female, Interferon-gamma, antagonists & inhibitors, pharmacology, Interleukin-4, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, OX40, agonists, T-Lymphocytes, Regulatory, Transforming Growth Factor beta1

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We report that OX40 stimulation drives all lineages of CD4 T cell development, including regulatory T cells (Tregs), and the plasticity of the response is dependant on local cytokines. In TGF-beta1-treated cultures, an OX40 agonist increased IFN-gamma and IL-4 production and diverted T cells from the Treg lineage. However, cytokine blockade in the context of OX40 stimulation promoted enhanced Treg accumulation. This observation was evident in naive mice, as OX40 engagement enhanced Treg proliferation and accumulation in vivo. Lastly, OX40 agonist administration influenced experimental autoimmune encephalomyelitis disease severity in opposing directions, depending on the timing of administration. Given during Ag priming, the OX40 agonist drove Treg expansion and inhibited disease, whereas given later it enhanced T cell effector cytokine production in the CNS and exacerbated disease. Hence, OX40 signaling can augment the accumulation of all CD4 T cell lineages; however, its accentuation of immune responses may have vastly different biologic outcomes depending upon the local cytokine milieu.

          Related collections

          Author and article information

          Journal
          19786544
          10.4049/jimmunol.0901112

          Comments

          Comment on this article