Cytokine Regulation of Natural Killer Receptors in Inhibiting Activated T Cell Function

In our extended studies, we have directly examined the expressions of various inhibitory natural killer cell Receptors (iNKRs) on Tumor-infiltrating lymphocytes (TILs) derived from human Cervical cancer (CC) by triple-color flow cytometry with combination of different surface markers. We found up-regulated expression of certain iNKRs (CD94/NKG2A) in TILs and in mixed lymphocyte-cancer cell cocultures. In our previous studies, we demonstrated that certain cytokines, including IL-10, TGF-beta (Sheu et al, Journal of Immunology, 2001, 167:2972-2978), and IL-15 (Sheu et al, Cancer Research, 2005, 65:2921-2929) can be expressed by CC cells. We further demonstrated that activated T cells bear iNKRs which inhibit cytotoxic activity. iNKRs are proposed to restrain the T cell receptor (TCR)-mediated cytolysis. We found that CC cells had altered HLA-A, -B, and -C molecules in a cancer microenvironment. The acquisition of both NK-like activity and expression of iNKRs by these T cells is parallel to prevent damage to normal host cells. However, there is also limited knowledge about the regulatory role of iNKR expression in T cell cytotoxicity.