In:
The Journal of Immunology, The American Association of Immunologists, Vol. 190, No. 1_Supplement ( 2013-05-01), p. 178.19-178.19
Abstract:
Together with T cell receptor recognition of cognate MHC-peptide complexes, signaling through OX40 promotes late-stage proliferation, survival, and enhanced memory formation of T cells. Despite its known role in co-stimulation, the intracellular signaling pathways regulated by OX40 are not well understood. Recently, we demonstrated that stimulation with an OX40 agonist increases Mnt protein levels by promoting Mnt protein stability. Mnt is thought to play a role in apoptosis, cell survival, and cell proliferation by opposing Myc activity through competition for binding to Max and shared target genes. Using siRNA-directed knockdown of Mnt, we demonstrated that Mnt is necessary for T cell survival ex vivo. In these current studies, we have examined the necessity of Mnt in OX40 signaling and function in the primary T cell response following vaccination. Using OX40-cre/ Mnt-floxed mouse model, we found that Mnt is required for the OX40-mediated enhancement of the primary CD4 T cell response following Listeria monocytogenes vaccination. In addition, we found that OX40 signaling decreased glucose uptake in T cells, a predicted consequence of Mnt upregulation and its antagonism of Myc-mediated glycolytic activity. Hence, future studies will examine if the glycolytic pathway is altered in Mnt knock-out T cells stimulated with OX40 agonists.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.190.Supp.178.19
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2013
detail.hit.zdb_id:
1475085-5
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