Regulation of cellular immune response against autologous human melanoma. II. Mechanism of induction and specificity of suppression.

The cytotoxic immune response in the peripheral blood lymphocytes (PBL) against an autologous malignant melanoma cell line, PJ-M, was found to be down-regulated in in vitro co-culture (IVC) selectively by unfractionated resident lymph node lymphocytes (derived from a lymph node infiltrated with the PJ-M melanoma cells) and T4+ as well as T8+ fractions of the resident lymph node-derived lymphocytes. In this study, the mechanism involved in, and the specificities of, cytotoxic immune response in this autologous system were examined at population and clonal levels. Resident lymph node lymphocytes were isolated from both involved and uninvolved lymph nodes from the same patient. Resident lymphocytes from both sources regulated the generation of cytotoxic immune response when both types of resident lymph node lymphocytes were further sensitized against the PJ-M cells in IVC and were expanded in interleukin 2 (IL 2). An IL 2-dependent homogeneous lymphocyte line (I-10:1) bearing the phenotype of a helper T cell (T4+) and a T4+ clone (I-10.3) of the I-10:1 line, established by limiting dilution culture, also down-regulated the generation of cytotoxic immune effector cells in the PBL in IVC against the PJ-M targets. The IL 2-dependent T4+ inducer line I-10:1 generated a functionally differentiated T8+ suppressor population(s) that, in turn, could abrogate cytotoxic response in fresh PBL in IVC against PJ-M cells. The inducer line I-10:1 and its subclone I-10.3 suppressed the generation of cytotoxic effector cells in the PBL in IVC selectively against the autologous PJ-M cells. Generation of cytotoxic allo-response in IVC was unaffected by the inducer lines. These results provide further evidence for the involvement of the regulatory network in cytotoxic immune response in an autologous human tumor system, and suggest a potential explanation for cytotoxic unresponsiveness against autologous melanoma cells.