Cross, but not direct, presentation of cell-associated virus antigens by spleen macrophages is influenced by their differentiation state

The initiation of T-cell immune responses requires professional antigen-presenting cells. Emerging data point towards an important role for macrophages (M phi) in the priming of naive T cells. In this study we analyzed the efficiency and the mechanisms by which M phi derived from spleen (Sp-M phi) or bone marrow (BM-M phi) present Lymphocytic choriomeningitis virus (LCMV) antigens to epitope-specific T cells. We demonstrate that because of phagosomal maturation, Sp-M phi downregulate their ability to cross-present cell-associated, but not soluble, antigens, as they are further differentiated in culture without altering their capacity to directly present virus antigens after infection. We propose that Sp-M phi are extremely efficient at direct and cross-presentation. However, if these cells undergo further M-CSF-dependent maturation, they will adapt to be more scavenger and phagocytic and concurrently reduce their cross-presenting capacity. Accordingly, Sp-M phi can have an important role in regulating T-cell responses through cross-presentation depending on their differentiation state. Immunology and Cell Biology (2010) 88, 3-12; doi:10.1038/icb.2009.90; published online 24 November 2009