T cell precursor frequency differentially affects CTL responses under different immune conditions.

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, 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.