Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4(+) T cell priming and Th1/Th2 cell restimulation

We have compared the efficiency of central nervous system and peripheral an tigen-presenting cells (APC) in T cell priming and restimulation. OVA pepti de 323-339-dependent activation of DO11.10 TCR-transgenic naive CD4(+) and polarized Th1 or Th2 cells was assessed in the presence of microglia and as trocytes from the neonatal mouse brain as well as dendritic cells (DC) and B cells purified from adult mouse lymph nodes. DC were the most efficient i n inducing naive T cell proliferation, IL-2 secretion and differentiation i nto Th1 cells, followed by IFN-gamma-preactivated microglia, large and smal l B cells. Astrocytes failed to activate naive T cells. IFN-gamma-pretreate d microglia were as efficient as DC in the restimulation of Th1 cells, wher eas IFN-gamma-pretreated astrocytes, large and small B cells were much less efficient. Conversely, Th2 cells were efficiently restimulated by all the APC types examined. During T cell priming, DC secreted more IL-12 than micr oglia but similar amounts of IL-12 were secreted by the two cell types upon interaction with Th1 cells. The hierarchy of APC established in this study indicates that DC and microglia are the most efficient in the stimulation of naive CD4(+) T cells and in the restimulation of Th1 cells, suggesting t hat activated microglia may effectively contribute to Th1 responses leading to central nervous system inflammation and tissue damage. These potentiall y pathogenic responses could be counteracted by the high efficiency of astr ocytes as well as microglia in restimulating Th2 cells.