Optimal induction of antigen-specific CD8+ T cell responses requires bystander cell participation

Efficient activation of specific immune responses requires a concerted interaction between T cells and antigen‐presenting cells. A requirement for bystander participation of CD4+ T cells for expansion and maintenance of memory CD8+ T cells has been noted in several models, but a role with regard to effector CD8+ T responses has not been well‐defined. In this report, the requirement of bystander participation for optimal induction of antigen‐specific CD8+ T cell effector function was determined by directly quantitating antigen‐specific interferon‐γ (IFN‐γ) CD8+ T cell responses by enzyme‐linked immunospot assays, and by indirectly evaluating induction of the chemokine monokine induced by IFN‐γ as a marker for IFN‐γ‐mediated effector function. Our results demonstrate that bystander cell participation, mediated by CD4+ T cell and natural killer (NK) cells, is required for optimal induction of antigen‐specific CD8+ T cell effector responses. Our data further establish a novel role for NK cells in the activation of antigen‐specific immune responses.