Research
Our lab works with the LP-BM5 murine retroviral isolate that causes immunodeficiency similar to AIDS. This disease is called murine AIDS (MAIDS) and is characterized by early polyclonal T and B cell activation and expansion, splenomegaly, lymphadenopathy and hypergammaglobulinemia, eventually leading to progressive immunodeficiency characterized by decreased T and B cell response susceptibility to opportunistic infections and increased incidence of B cell lineage lymphomas. We have discovered an immunodominant cytolytic T lymphocyte (CTL) epitope encoded in a previously un-recognized LP-BM5 retroviral alternative (+1 NT) gag translational open reading frame. CTLs from MAIDS-resistant BALB/c mice specific for this cryptic gag epitope are the basis of protection from LP-BM5-induced MAIDS in BALB/c mice. The inability of B6 mice to mount an anti-gag CTL response is critical to MAIDS pathogenesis. Our lab looks to explore both the immunological response to LP-BM5 infection and also viral pathogenesis.
Current projects in the lab examine both innate and adaptive immune response to LP-BM5 infection and how these influence LP-BM5 infection and MAIDS:
- Myeloid Derived Suppressor Cells: We have identified a monocytic subset of MDSCs that increases in the spleens of LP-BM5 infected mice, and which suppresses in vitro B and T cell proliferation. Recently a study of HIV- related MDSCs has been published, reinforcing our thoughts of the relevance of our MDSC related studies. The lab is further characterizing these cells and understanding the suppressive mechanisms utilized by MDSCs and also how they emerge in the LP-BM5 retroviral model.
- Cytolytic T Lymphocytes (CTLs): In the LP-BM5 retroviral model, CTLs from resistant strains of mice can mount an effective response against primary LP-BM5 infection, resulting in no viral pathogenesis/MAIDS. We can prime these CTLs to kill LP-BM5 infected cells, transfer these CTLs into MAIDS-susceptible (CD8-/-) mice, and these CTLs will protect the mice from MAIDS. However, upon secondary infection, either in the original CD8-/- recipient mouse or after the CTLs have been transferred and protected the original recipient mouse and then subsequently transferred into a new, not previously infected mouse, they are unable to protect from MAIDS disease. Currently, we are looking into why this happens, and how we can better establish durable memory responses so that the CTLs protect susceptible mice from more than one infection with LP-BM5.
- Innate Immune Responses: Little is known regarding the innate immune responses to LP-BM5 infection. We are investigating the role of innate immune responses, including Type I interferon (IFN) production and induction of indoleamine 2,3-dioxygenase (IDO), in MAIDs. We are working on determining how and when LP-BM5 triggers these innate immune responses to better understand viral pathogenesis.