Role of T-cell subsets in the destruction of established metastases of 13762A rat mammary adenocarcinoma

Abstract

The 13762A rat mammary adenocarcinoma metastasizes with high frequency to regional lymph nodes and lungs. The intratumoral injection of Corynebacterium parvum on day 7 followed by primary tumor excision on day 20 significantly prolonged survival and cured 10-40% of syngeneic F344 rats. Established metastases were destroyed by the treatment, and strong and specific tumor rejection immunity was induced. The purpose of the present study was to determine if T-cells were required for the C. parvum treatment to be effective and to identify the subsets of T-lymphocytes that might participate in the response. The results indicated that rats depleted by either neonatal thymectomy or a combination of adult thymectomy, 900 rad, and bone marrow reconstitution did not inhibit tumor growth after C. parvum treatment. Restoration of depleted rats with lymph node cells permitted effective treatment. The lymph node cells that were responsible for restoration expressed both W3/13 (pan-T-cell) and W3/25 (helper T-cell) membrane-associated differentiation antigens. T-cells that bore the MRC OX8 (cytotoxic-suppressor T-cell) antigen did not restore the response to C. parvum treatment. The effect of lymph node restoration was markedly potentiated by simultaneous administration of thymocytes, a T-cell population that expresses both W3/25 and MRC OX8 antigens. In conclusion, the cytotoxic-suppressor T-cells were ineffective in the restoration of T-cell-depleted, tumor-bearing rats to benefit from C. parvum but helper T-cells were highly effective, and their activity was strongly potentiated by administration of thymocyte amplifier cells.