T-CELL-DERIVED IL-3 INDUCES THE PRODUCTION OF IL-4 BY NON-B-CELL, NON-T-CELL TO AMPLIFY THE TH2-CYTOKINE RESPONSE TO A NON-PARASITE ANTIGENIN SCHISTOSOMA-MANSONI-INFECTED MICE

We describe a novel amplification mechanism underlying the increased e arly IL-4 production observed in Schistosoma mansoni-infected mice in response to a non-parasite Ag, sperm whale myoglobin (SwMb). Earlier s tudies have shown that splenic Fc epsilon R(+) non-B, non-T (NBNT) cel ls from schistosome-infected mice secrete IL-4 after stimulation with parasite Ag. We now demonstrate that purified NBNT cells from SwMb-imm unized S. mansoni-infected mice do not respond directly to SwMb, but p roduce IL-4 in response to IL-3. Accordingly, we show that the early S wMb-specific IL-4 response of spleen cells (SC) from immunized infecte d mice is dependent on IL-3 and on CD4(+) T cells. Thus, most of the e arly SwMb-induced IL-4 from SC of infected mice appears to be produced by NBNT cells triggered by IL-3 synthesized by SwMb-specific CD4(+) T cells. IL-3-induced IL-4 production was also observed in purified NBN T cells from immunized uninfected mice, but the frequency and/or IL-4- producing capacity of splenic IL-3-responsive cells was found to be 8 to 16 times higher in immunized infected animals, IL-4 production by p urified CD4(+) cells from immunized infected mice was also seen after SwMb stimulation, but this response showed slower kinetics than those of total SC, was IL-3-independent, and on average threefold greater th an that by CD4(+) cells from immunized uninfected controls. Thus, incr eased SwMb-induced IL-4 production in immunized S. mansoni-infected mi ce results from direct synthesis by CD4(+) T cells, as well as their s timulation via IL-3 of an expanded population of NBNT cells. The latte r pathway may serve as an amplification loop for Th2-cytokine response s.