Cytokine production by memory T cells in secondary immune responses has a critical role in host defenses. Previously, we had demonstrated that a unique antigen composed of sialyl lewis(x) (sLe(x)) was expressed on CD45RO(+) memory-phenotype subsets of human T cells. Here, we found that the sLe(x) antigen was up-regulated on CD45RA(+) naïve human CD4(+) T and CD8(+) T cells by TCR stimulation. In addition, sLe(x) antigen-expressing CD4(+) T and CD8(+) T cells in human PBMCs were activated immediately by cytokine stimulations composed of IL-2 plus IL-12 or IL-15 in an antigen-independent manner. Moreover, the sLe(x)-positive human CD8(+) T cells significantly enhanced reverse antibody-dependent cellular cytotoxicity compared with a sLe(x)-negative population. These findings clearly indicate that sLe(x) antigen-expressing memory phenotype CD4(+) T and CD8(+) T cells contribute to early-stage immunity by providing a source of IFN-gamma and cytotoxicity, suggesting that they would be a key immunomodulator in host defenses.