Naive CD8+ T cells integrate signals from peptide antigen-MHC complex (pMHC; signal 1), costimulatory molecules (signal 2), and cytokines (signal 3) upon their interaction with antigen-presenting dendritic cells (DCs). Despite the vast knowledge on molecular regulators of effector CD8+ T cell responses, it remains elusive whether CD8+ T cells integrate all signals from a single interacting DC or whether additional DCs are required for exponential expansion of CD8+ T cells. To address this question, we combined conventional flow cytometry with intravital two-photon microscopy (2PM) and light sheet fluorescence microscopy of lymph nodes (LNs) in a DC vaccination model. Subcutaneous injection of at least 20,000 peptide-pulsed DCs induced exponential expansion of a starting population of 15–25 antigen-specific CD8+ cells, which corresponded to a DC : T cell ratio of 8 or more in draining LNs. We then analyzed the effect of pMHC-negative “bystander” DCs as supplement for pMHC+ DCs, keeping the total number of injected DCs to 20,000. In the presence of bystander DCs, injection of as few as 1,250 pMHC-carrying DCs (corresponding to 20 pMHC+ DCs per popliteal LN) sufficed for exponential expansion and effector differentiation of CD8+ cells. 2PM imaging showed that the rescue of T cell expansion by bystander DCs was independent of direct interactions. In contrast, Il12a–/– bystander DCs did not potentiate expansion of CD8+ cells, indicating that bystander DCs augment antigen-specific CD8+ T cell responses via secretion of inflammatory cytokines. In sum, our results demonstrate that activated DCs that do not present cognate pMHC significantly lower the pMHC requirement for exponential expansion of responding CD8+ T cells. Furthermore, our data suggest that CD8+ T cell expansion follows a “coincidence detection” model in which cognate interaction with single DCs do not suffice without additional signal 3 from the surrounding immune microenvironment.