TY - JOUR
T1 - Cutting edge
T2 - OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right
AU - Ruby, Carl E.
AU - Yates, Melissa A.
AU - Hirschhorn-Cymerman, Daniel
AU - Chlebeck, Peter
AU - Wolchok, Jedd D.
AU - Houghton, Alan N.
AU - Offner, Halina
AU - Weinberg, Andrew D.
PY - 2009/10/15
Y1 - 2009/10/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77949654340&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949654340&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0901112
DO - 10.4049/jimmunol.0901112
M3 - Article
C2 - 19786544
AN - SCOPUS:77949654340
SN - 0022-1767
VL - 183
SP - 4853
EP - 4857
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -