In an attempt to understand the basis of lowered natural killer (NK) and T cell functions in unaffected members from cancer families, we investigated cytotoxic T lymphocyte function (CD3-directed lysis) and the ability of the lymphocytes to respond to cytokines such as IL-2, IFN-α and IL-12. We observed lower CD3-mediated cytotoxic activity in these individuals supported by significantly lower numbers of circulating CD3+ lymphocytes. The cytokine treatment studies revealed impaired response to IFN-α and IL-12 in unaffected members and breast cancer patients. The observations presented herein not only reinforce our earlier finding that lower NK and T lymphocyte function may be a feature of cancer families, but also suggest that such impaired responses may be one of the factors contributing to lower cytotoxic potential of the circulating lymphocytes.
