T cell precursor frequency differentially affects CTL responses under different immune conditions.
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, Ia(b-/-) gene knockout and transgenic RIP-mOVA mice, and assessed OVA-pulsed DC (DC(OVA))-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 DC(OVA)-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.
Ye
Zhenmin
Z
Research Unit, Saskatchewan Cancer Agency, 20 Campus Drive, Saskatoon, Saskatchewan, Canada.
Ahmed
Khawaja Ashfaque
KA
Huang
Junqiong
J
Xie
Yufeng
Y
Munegowda
Manjunatha Ankathatti
MA
Xiang
Jim
J
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology*