TYPE-1 CD8(-CELL RESPONSES DURING INFECTION WITH THE HELMINTH SCHISTOSOMA-MANSONI() T)

IL-4 promotes the development of type 2 CD8(+) T cells. In mice infect ed with the helminth Schistosoma mansoni, the Th response is overtly T h2-like, creating an environment rich in IL-4. Consequently, we examin ed whether CD8(+) subset development in schistosome-infected mice is b iased in a type 2 direction; this is of interest because CD8(+) cells have been proposed to play an immunoregulatory role during schistosomi asis. Contrary to expectation, our data indicate that the CD8(+) cell response in infected mice is strongly type 1-like. Thus, infection wit h S. mansoni leads to the development of concurrent Th2 and type 1 CD8 (+) cell responses. Cytokine production by type 1 CD8(+) cells is depe ndent upon help from CD4(+) cells; this helper activity can be substit uted by exogenous IL-2 or IL-4. Since Th cells from infected mice make little IL-2 but large amounts of IL-4, we propose that IL-4 is likely to be the physiologic mediator of help in infected animals, a view su pported by the ability of mAbs against IL-4R and IL-4 to reduce IFN-ga mma production by splenocytes in vitro. CD8(+) cells from infected mic e are able to produce IFN-gamma in response to schistosome Ag presente d by bone marrow-derived APC. A regulatory role for the CD8(+) cells i s implied by the observation that CD8(+) cell-depleted splenocytes fro m infected mice exhibit increased proliferative responses and IL-4 pro duction in response to mAb anti-CD3. These findings suggest that in mi ce infected with schistosomes there exists a regulatory pathway in whi ch type 1 CD8(+) cells, under the control of IL-4, dampen immunopathol ogic type 2 responses.