Neutrophils and T cells often co-infiltrate pathological tissues, which suggests that these 2 cell types may interact with each other. Over the years, in vitro studies have demonstrated that neutrophils and T cells are capable of modulating each other's responses. However, few studies have examined the cross-talk between human neutrophils and CD8(+) T cells, although murine models clearly show the critical role of their interaction in bacterial infections and cancer. Herein, we evaluated the interaction between human neutrophils and CD8(+) T cells in a coculture system using highly purified cell preparations and compared the responses to ones from cocultures of neutrophils and CD4(+) T cells. We report that anti-CD3-activated CD4(+) and more potently, anti-CD3-activated CD8(+) T cells modulate apoptosis and expression of activation markers by neutrophils, and neutrophils have no or little effect on T cell survival, expression of surface markers, and cytokine release. The observed effects of CD8(+) T cells on neutrophils were mainly attributable to the release of TNF-alpha, IFN-gamma, and GM-CSF, and the effects of CD4(+) T cells involved IFN-gamma and GM-CSF production. This study expands our knowledge of the molecular bases, whereby human CD4(+) and CD8(+) T cells modulate neutrophil survival and antigen expression. J. Leukoc. Biol. 88: 1163-1170; 2010.