The role of macrophages and bone marrow-derived dendritic cells in the rejection of fetal thymus allografts.

Deoxyguanosine (dGuo)-treated fetal thymus lobes are capable of prolonged survival in histoincompatible recipients despite their expression of both class I and class II major histocompatibility complex (MHC) antigens. Although dGuo treatment has been directly shown to eliminate lymphocytes from the lobes its effect upon other marrow-derived passenger cells such as macrophages and dendritic cells is less well defined. Here we show that dGuo-treated CBA(H-2k) fetal thymus lobes allowed to develop under the renal capsule of immunoincompetent BALB/c (H-2d) mice for 3 weeks are depleted of donor-type dendritic cells in contrast to grafts of untreated lobes where donor-derived dendritic cells are still detectable at this time. Moreover, dGuo-treated thymus lobes underwent prompt allo-rejection if recolonized with donor-type dendritic cells prior to transplantation into immunocompetent recipients. Together with our observation that macrophages (or their precursors) survive dGuo treatment, these results suggest that the reduced immunogenicity of fetal thymus grafts seen following dGuo treatment is related to dendritic cell, rather than macrophage depletion.