Preferential infection of immature dendritic cells and B cells by mouse mammary tumor virus.
Until now it was thought that the retrovirus mouse mammary tumor virus preferentially infects B cells, which thereafter proliferate and differentiate due to superantigen-mediated T cell help. We describe in this study that dendritic cells are infectable at levels comparable to B cells in the first days after virus injection. Moreover, IgM knockout mice have chronically deleted superantigen-reactive T cells after MMTV injection, indicating that superantigen presentation by dendritic cells is sufficient for T cell deletion. In both subsets initially only few cells were infected, but there was an exponential increase in numbers of infected B cells due to superantigen-mediated T cell help, explaining that at the peak of the response infection is almost exclusively found in B cells. The level of infection in vivo was below 1 in 1000 dendritic cells or B cells. Infection levels in freshly isolated dendritic cells from spleen, Langerhans cells from skin, or bone marrow-derived dendritic cells were compared in an in vitro infection assay. Immature dendritic cells such as Langerhans cells or bone marrow-derived dendritic cells were infected 10- to 30-fold more efficiently than mature splenic dendritic cells. Bone marrow-derived dendritic cells carrying an endogenous mouse mammary tumor virus superantigen were highly efficient at inducing a superantigen response in vivo. These results highlight the importance of professional APC and efficient T cell priming for the establishment of a persistent infection by mouse mammary tumor virus.
Vacheron
Sonia
S
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Luther
Sanjiv A
SA
Acha-Orbea
Hans
H
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000637:transplantation / Q000821:virology*; D007399:Interphase / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012192:Retroviridae Infections / Q000276:immunology; D018089:Superantigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D014412:Tumor Virus Infections / Q000276:immunology
D018089:Superantigens