Macrophages induce cellular immunity by activating Th1 cell responses and suppressing Th2 cell responses

Differentiation of naive CD4+ T cells (Th0) into Th1 or Th2 cells determines whether antigen will raise a cellular or a humoral immune response. The maturation pathway chosen by the Th0 cell is often decisive for the outcome of disease and depends among others on the (co-)stimulatory attributes of the APC and the nature and abundance of cytokines provided by the APC and the microenvironment. In this study, we used macrophages, loaded ex vivo with antigen, for inciting Th0 activation and differentiation in vivo. The macrophages were derived from a clonal, immortalized population that both functionally and phenotypically expressed features characteristic of mature macrophages. Injection into syngeneic mice of IFN-gamma-treated, Ag-loaded macrophages induced a primary T cell response, indicated by the occurrence of a proliferative response in vitro after restimulation of splenocytes with Ag. Analysis of the accompanying cytokine secretion revealed high numbers of IFN-gamma-producing Th1 cells and only a few IL-4-secreting Th2 cells. This dominance of Th1 cells had functional implications, reflected in the high titer of Th1 cell-dependent IgG2 Abs and the absence of IgG1, characteristic of humoral immunity. Moreover, administration of Ag-loaded macrophages to mice with an ongoing Th1/Th2 response resulted in a complete suppression of IgG1 production, whereas IgG2 levels remained unaffected. These results demonstrate that macrophages exert APC activity in the organism, strongly skew primary responses to cellular immunity, and in addition suppress an already generated Th2-dependent humoral response, thus characterizing these cells as Th1-oriented APC.