CIRCULATING LEVELS OF IL-10 ARE CRITICALLY RELATED TO GROWTH AND REJECTION PATTERNS OF MURINE MASTOCYTOMA-CELLS

Previously tumorigenic P815 tumor cells are rejected by histocompatibl e mice after transfection with a mutated retroviral gene, and the host is made resistant to subsequent challenge with tumorigenic (control) cells transfected with the nonmutated sequence. To functionally charac terize the class I-restricted response to the tumor cell vaccine, we h ave assessed the in vitro (by CD8(+) cells) and in vivo production of type 1 or type 2 cytokines in mice injected with either type of transf ected P815 derivative. IL-12 and IL-IO were selectively or preferentia lly expressed by the regressor mice, and this correlated with the dete ction of functional type 1 reactivity in vivo (i.e., delayed-type hype rsensitivity). Other cytokines were produced by the regressor mice onl y in vitro (IFN-gamma) or were not detected at all with either type of tumor recipient (IL-4). By means of monoclonal antibody-mediated neut ralization or enhancement of endogenous cytokine levels, IL-IO was fou nd to serve an important role in the growth and rejection patterns of the transfected P815 derivatives. In addition to previous evidence for an IL-12 requirement in promoting anti-P815 reactivity, these data es tablish IL-10 as an important cytokine in permitting optimal expressio n of this reactivity, which apparently develops in the absence of a st rong bias toward a type 1 or type 2 cytokine response. (C) 1997 Academ ic Press.