Cutting edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right Journal Article
| Authors: | Ruby, C. E.; Yates, M. A.; Hirschhorn-Cymerman, D.; Chlebeck, P.; Wolchok, J. D.; Houghton, A. N.; Offner, H.; Weinberg, A. D. |
| Article Title: | Cutting edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right |
| 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-β1-treated cultures, an OX40 agonist increased IFN-γ 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. Copyright © 2009 by The American Association of Immunologists, Inc. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; cell proliferation; animal cell; mouse; cell maturation; interleukin 4; animal experiment; central nervous system; cell lineage; regulatory t lymphocyte; th2 cell; disease severity; immune response; gamma interferon; cd4+ t lymphocyte; transforming growth factor beta1; cytokine production; cd4 antigen; th1 cell; disease exacerbation; cell expansion; cd134 antigen; ox40 antigen agonist; allergic encephalomyelitis |
| Journal Title: | Journal of Immunology |
| Volume: | 183 |
| Issue: | 8 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2009-10-15 |
| Start Page: | 4853 |
| End Page: | 4857 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0901112 |
| PROVIDER: | scopus |
| PUBMED: | 19786544 |
| PMCID: | PMC4625917 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 7" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus" |
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