THE DENSITY OF THE CLASS-II MHC T-CELL RECEPTOR-LIGAND INFLUENCES IFN-GAMMA IL-4 RATIOS IN IMMUNE-RESPONSES IN-VIVO/

Activation of CD4(+) T cells depends on T cell receptor recognition of MHC class II/peptide and on costimulation provided by CD28/B7. It has been shown that different levels of costimulation can influence T hel per cell differentiation into Th1 versus Th2 phenotypes. Similar argum ents have been made for different levels of peptide/MHC density on ant igen-presenting cells, but to date supportive evidence has only come f rom in vitro studies. Here, using transgenic mice with reduced MHC cla ss II expression on both B cells and dendritic cells, we demonstrate t hat T helper cell differentiation in vivo is also influenced by the de nsity of expression of MHC class II. Although priming and expansion of antigen-specific T cells were normal in these mice, T cell responses were dominated by the Th1-associated cytokine IFN-gamma, with reduced levels of the Th2 cytokine IL-4 compared to controls. These results pr ovide direct evidence that the efficiency of antigen presentation in v ivo can determine effector cell phenotype. (C) 1998 Academic Press.