Induction of tumor immunity by removing CD25(+)CD4(+) T cells: A common basis between tumor immunity and autoimmunity

This study shows that removal of a T cell subpopulation can evoke effective tumor immunity in otherwise nonresponding animals, Elimination of CD25-exp ressing T cells, which constitute 5-10% of peripheral CD4(+) T cells in nor mal naive mice, elicited potent immune responses to syngeneic tumors in viv o and eradicated them. The responses were mediated by tumor-specific CD8(+) CTLs and tumor-nonspecific CD4(-)8(-) cytotoxic cells akin to NK cells, Fu rthermore, in vitro culture of CD25(+)4(+) T cell-depleted splenic cell sus pensions prepared from tumor-unsensitized normal mice led to spontaneous ge neration of similar CD4(-)8(-) cytotoxic cells capable of killing a broad s pectrum of tumors; reconstitution of CD25(+)4(+) T cells inhibited the gene ration, In this culture, self-reactive CD25(-)4(+) T cells responding to se lf peptides/class II MHC complexes on APCs spontaneously proliferated upon removal of CD25(+)4(+) T cells, secreting large amounts of IL-2. The IL-2 t hus produced appeared to be responsible for the generation of CD4(-)8(-) NK cells as lymphokine activated killer cells, because direct addition of an equivalent amount of IL-2 to the culture of CD4(-)8(-) cells generated simi lar lymphokine-activated killer/NK cells, whereas coculture of normal CD4(- )8(-) cells with CD25(-)4(+) T cells from IL-2-deficient mice did not. Thus , removal of immunoregulatory CD25(+)4(+) T cells can abrogate immunologica l unresponsiveness to syngeneic tumors in vivo and in vitro, leading to spo ntaneous development of tumor-specific effector cells as well as tumor-nons pecific ones. This novel way of evoking tumor immunity would help to devise effective immunotherapy for cancer in humans.