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 (Mphi) in the priming of naïve T cells. In this study we analyzed the efficiency and the mechanisms by which Mphi derived from spleen (Sp-Mphi) or bone marrow (BM-Mphi) present Lymphocytic choriomeningitis virus (LCMV) antigens to epitope-specific T cells. We demonstrate that because of phagosomal maturation, Sp-Mphi 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-Mphi 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-Mphi can have an important role in regulating T-cell responses through cross-presentation depending on their differentiation state.