DENDRITIC CELLS AND MACROPHAGES ARE REQUIRED FOR TH1 DEVELOPMENT OF CD4-CELLS FROM ALPHA-BETA-TCR TRANSGENIC MICE - IL-12 SUBSTITUTION FOR MACROPHAGES TO STIMULATE IFN-GAMMA PRODUCTION IS IFN-GAMMA-DEPENDENT( T)

We have examined the antigen presenting cell (APC) requirements for pr imary T cell activation and T helper (Th) cell phenotype differentiati on using naive CD4+ T cells from alphabeta TCR transgenic mice. Purifi ed dendritic cells were the principal cell required for induction of p rimary ovalbumin peptide specific T cell activation and clonal expansi on. However, dendritic cells did not induce differentiation of T cells toward Th1 or Th2 phenotype. Addition of IL-4 during primary dendriti c cell stimulations of T cells resulted in the development of a Th2 ph enotype which produced high levels of IL-4 during secondary and tertia ry stimulation. In contrast, development of Th1 cells producing high l evels of IFN-gamma could not be induced with dendritic cells alone but required the addition of appropriately activated macrophages. Additio n of splenic or peritoneal B cells did not induce Th1 development. Act ivated splenic macrophages induced Th1 development via a non-MHC restr icted mechanism. Thus, requirements for induction of proliferation of naive CD4+ T cells are distinct from those directing Th1 phenotype dev elopment. IL-12 could replace the requirement for macrophages to induc e Th1 development when T cells were activated with dendritic cells. Fu rthermore, this IL-12 mediated development of Th1 cells producing high levels of IFN-gamma was dependent on IFN-gamma.