Development and persistence of cytolytic T lymphocytes in regressing or progressing Moloney sarcomas

Abstract

Intratumoral T lymphocytes were recovered sequentially after induction of regressing or progressing Moloney sarcomas in BALB/c mice and were assayed quantitatively for their ability to kill specifically the tumor (MSC) cells used for induction. The cytolytic activities of the two lymphocyte populations described two distinct biphasic kinetic profiles that were similar in amplitude and duration but separated from each other by 4-6 days. In progressing neoplasm, there was a rapidly occuring accumulation of T lymphocytes highly cytolytic for MSC cells. This response, however, was not sustained and disappeared in association with the onset of unchecked tumor growth. In contrast, T lymphocyte cytolytic activity developed more slowly in regressing sarcomas and attained peak levels coincident with the beginning of tumor regression. Similar changes in cytolytic activity characterized T lymphocytes in lymph nodes draining tumors. When cultured in vitro for 4 days, non-cytotoxic T lymphocytes from regional lymph nodes draining progressing sarcomas regained very high levels of cytolytic activity. Such restitution was diminished, however, if MSC cell lysates, macrophages or macrophages fed MSC cell lysates were present during the culture period. These experiments provided presumptive evidence that T lymphocyte-mediated cytolytic activity was lost in progressively growing Moloney sarcomas as a consequence of suppression in vivo of the genesis and/or functional expression of cytolytic T lymphocytes, perhaps by macrophages and/or soluble tumor antigen.