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A role of ITK (interleukin 2–inducible T cell kinase) in the temporal kinetics of gene regulation in CD8 T cells 4266

Year: 2025
Type: article
Abstract: Description The role of ITK in the regulation of early activation factors such as NFAT, NF-kb, and AP-1 has been widely characterized. ITK is not essential to the signaling cascade initiated after TCR stimulation, but instead tunes graded CD8+ T cell responses after stimulation with antigens of varying affinities. Utilizing a TCR transgenic OT-1 timed fluorescent reporter “Nr4a3-Tocky” mouse model bred to an ITK -/- we visualized the expression of cell fate and cell trafficking markers in bulk splenocytes at 5, 12, 24, 48, and 72 hours after TCR stimulation with high and low affinity peptide ligands in vitro. Time courses with ITK inhibitor added at 24 hours post-peptide addition were also done. ITK -/- CD8+ T cells showed decreased expression of the Nr4a3-tocky reporter, IRF4, IRF8, cMyc, and Egr2 at 5 hrs post peptide addition while at 48 hours showed increased expression compared to WT. WT CD8+ T cells stimulated with high or low affinity peptide showed different magnitude of CD44, CD69, CD25, IRF4, IRF8, cMyc, and EGR2 but the same pattern of kinetics over time, indicating varying peptide affinity is not responsible for differences in expression. When ITK inhibitor was added 24 hrs post peptide addition little effect on persistent expression was seen leading to the hypothesis that these effects are a consequence of early signaling events. This persistence of expression shows a possible discordance between the negative feedback signals a CD8 T cell receives with and without ITK. Funding Sources This work was supported by the NIH/NIAID (R01 AI043957). The Barbara Davis Center Cell and Tissue Analysis Core at the University of Colorado Diabetes Research Center (funded by NIH/NIDDK P30-DK116073) were also utilized. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)
DOI: 10.1093/jimmun/vkaf283.1967
Authors: Josh J. Hunkins, Zoe K. Bedrosian, Uddeep Chaudhury, Alayna M. Rosales, Masahiro Ono, Leslie J. Berg
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416447424
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