T cell precursor frequency differentially affects CTL responses under different immune conditions |
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Authors: | Ye Zhenmin Ahmed Khawaja Ashfaque Huang Junqiong Xie Yufeng Munegowda Manjunatha Ankathatti Xiang Jim |
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Institution: | Research Unit, Saskatchewan Cancer Agency, 20 Campus Drive, Saskatoon, Saskatchewan, Canada S7N 4H4 |
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Abstract: | Generation of effective CTL responses is the goal of many vaccination protocols. However, to what extant T cell precursor frequencies will generate a CD8+ CTL response has not been elucidated properly. In this study, we employed a model system, in which naive CD4+ and CD8+ T cells derived from ovalbumin (OVA)-specific TCR transgenic OT II and OT I mice were used for adoptive transfer into wild-type, Iab−/− gene knockout and transgenic RIP-mOVA mice, and assessed OVA-pulsed DC (DCOVA)-stimulated CD8+ CTL responses in these mice. We demonstrated that (i) a critical threshold exists above which T cells precursor frequency cannot enhance the CTL responses in wild-type C57BL/6 mice, (ii) increasing CD8+ T cell precursors is required to generate CTL responses but with functional memory defect in absence of CD4+ T cell help, and (iii) increasing CD4+ and CD8+ T cell precursors overcomes immune suppression to DCOVA-stimulated CD8+ CTL responses in transgenic RIP-mOVA mice with OVA-specific self immune tolerance. Taken together, these findings may have important implications for optimizing immunotherapy against cancer. |
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Keywords: | CTL response CD4+ CD8+ T cell precursors Transgenic RIP-mOVA mice |
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