TYPE-1 VERSUS TYPE-2 CYTOKINE RELEASE BY V-BETA T-CELL SUBPOPULATIONSDETERMINES IN-VIVO ANTITUMOR REACTIVITY - IL-10 MEDIATES A SUPPRESSIVE ROLE

We have previously reported that CD8(+) tumor-draining lymph node (TDL N) cells activated with anti-CD3 and IL-2-mediated tumor regression in adoptive immunotherapy, In this study, we examined the TCR V beta rep ertoire usage of TDLN cells with respect to cytokine release profiles and therapeutic efficacy in vivo, The majority of the whole population of TDLN cells after activation with anti-CD3 were composed of V beta 3(+), -5(+), -7(+), -8(+), and -11(+) cells. Enrichment of V beta subs ets of TDLN cells by in vitro activation with anti-V beta mAb revealed V beta 8(+) cells released high amounts of IFN-gamma and granulocyte/ macrophage-CSF (CM-CSF) with minimal amounts of IL-10 in response to t umor and mediated tumor regression in vivo. In contrast, enriched popu lations of V beta 5(+), V beta 7(+), and V beta 11(+) cells released l ow amounts of IFN-gamma and GM-CSF with high levels of IL-10 and had n o in vivo antitumor reactivity, In vitro depletion of specific V beta subsets from the whole TDLN pool confirmed that the profile of cytokin es released correlated with in vivo antitumor function. Therapeutic ef ficacy mediated by TDLN cells required the release of IFN-gamma and CM -CSF since in vivo neutralization of both cytokines inhibited tumor re gression, The administration of anti-IL-10 mAb abrogated the suppresse d antitumor response manifested by adoptively transferred TDLN cells, which elaborated increased levels of IL-10, Our study documents that t ype 1 cytokine release (i,e,, IFN-gamma and CM-CSF) promotes in vivo t umor Ag recognition, in contrast to type 2 release (i,e,, IL-10), whic h suppresses this interaction, and discriminates the functional activi ty of V beta subpopulations of effector cells.