INTERFERON-GAMMA-PRODUCING AND INTERLEUKIN-4-PRODUCING T-CELLS CAN BEPRIMED ON DENDRITIC CELLS IN-VIVO AND DO NOT REQUIRE THE PRESENCE OF B-CELLS

The antigen-presenting cell (APC) requirements for the in vivo inducti on of Th1 and Th2-type responses were investigated using a severe comb ined immunodeficiency (SCID)mouse chimera model. SCID mice adoptively transferred with either T cells [SCID(T)] or T + B cells [SCID(T + B)] and immunized with antigen in adjuvant were able to generate antigen- specific T cells which could produce both interferon (IFN)-gamma and i nterleukin (IL)-4 upon in vitro restimulation. This suggests that B ce ll APC are not necessary for the priming of either IFN-gamma- or IL-4- producing T cells in vivo. The ability of different APC to activate Th 2-dependent effector mechanisms was also investigated. SCID(T) and SCI D(T + B) mice were infected with the nematode parasite Nippostrongylus brasiliensis and analyzed for the development of IL-5-dependent perip heral blood eosinophilia. Following infection both SCID(T) and SCID(T + B) mice generated similar numbers of peripheral blood eosilnophils, suggesting that similar amounts of IL-5 had been produced. Therefore, B cell APC are also not required for the in vivo activation of Th2 cel ls to lymphokine production. To establish more precisely which APC pri me T cells to produce IFN-gamma and IL-4, normal mice were immunized b y injection of syngeneic splenic dendritic cells which had been pulsed with antigen in vitro. T cells from these immunized mice were able to produce good IFN-gamma and IL-4 responses upon in vitro restimulation with specific antigen; therefore, dendritic cells appear to be suffic ient APC for the in vivo priming of both IFN-gamma- and IL-4-producing T cells.