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

Abstract

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- (IFN-) CD8 T cell responses by enzyme-linked immunospot assays, and by indirectly evaluating induction of the chemokine monokine induced by IFN- as a marker for IFN--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. J. Leukoc. Biol. 72: 1164–1171; 2002