Sequential T Cell Response Involved in Tumor Rejection of Sarcoma, Meth A, in Syngeneic Mice

We investigated the type of T cell response involved in Meth A tumor rejection in primary immune and hyperimmune syngeneic mice. It was found that a CD4(+) T cell‐mediated delayed‐type hypersensitivity (DTH) response activating non‐specific killer cells such as macrophages, NK and LAK cells, without a specific CD8(+) cytotoxic T lymphocyte (CTL) response, was the major immune response leading to Meth A tumor rejection in primary immune mice. In contrast, the specific CD8(+) CTL response was the major response leading to the tumor rejection, in addition to CD4(+) T cell‐mediated DTH response, in hyperimmune mice. Analysis of CD4(+) T cell clones established from primary immune and hyperimmune spleen cells indicated that a CD4(+) T cell clone (C9) of primary immune mice (although only one clone was established) was of Th1 type, and induced cytotoxicity in accessory cells by classic DTH in vitro. Eight CD4(+) T cell clones were established from hyperimmune spleen cells. Six out of the eight clones were of the Th2 type and two were Th0‐like. However, no Th1‐type CD4(+) T cell clone was established from hyperimmune spleen cells. All of these CD4(+) T cell clones, even the Th2‐type clones, were capable of inducing cytotoxicity in vitro in T cell‐depleted accessory cells, as in an in vitro DTH response. We postulate on the basis of these results that the T cell response leading to Meth A tumor rejection in vivo sequentially changed from a CD4(+) T cell‐mediated classic DTH response to a CD8(+) CTL response, in addition to a cellular response mediated probably by Th2‐type cells, during the process of repeated immunization.