In vivo dendritic cell depletion reduces breeding efficiency, affecting implantation and early placental development in mice.

Implantation of mammalian embryos into their mother's uterus ensures optimal nourishment and protection throughout development. Complex molecular interactions characterize the implantation process, and an optimal synchronization of the components of this embryo-maternal dialogue is crucial for a successful reproductive outcome. In the present study, we investigated the role of dendritic cells (DC) during implantation process using a transgenic mouse system (DTRtg) that allows transient depletion of CD11c+ cells in vivo through administration of diphtheria toxin. We observed that DC depletion impairs the implantation process, resulting in a reduced breeding efficiency. Furthermore, the maturity of uterine natural killer cells at dendritic cell knockout (DCKO) implantation sites was affected as well; as demonstrated by decreased perforin expression and reduced numbers of periodic-acid-Schiff (PAS)-positive cells. This was accompanied by disarrangements in decidual vascular development. In the present study, we were also able to identify a novel DC-dependent protein, phosphatidylinositol transfer protein beta (PITPbeta), involved in implantation and trophoblast development using a proteomic approach. Indeed, DCKO mice exhibited substantial anomalies in placental development, including hypocellularity of the spongiotrophoblast and labyrinthine layers and reduced numbers of trophoblast giant cells. Giant cells also down-regulated their expression of two characteristic markers of trophoblast differentiation, placental lactogen 1 and proliferin. In view of these findings, dendritic cells emerge as possible modulators in the orchestration of events leading to the establishment and maintenance of pregnancy.

Production of Peptide of Retroviral Origin in Sera of Patients with Chronic Myeloid Leukemia at Acute Phase.

In the present study we investigated production of the peptide of retroviral origin in patients with various types of leukemia. For this purpose the high affinity rabbit antibodies were generated against the synthetic peptide representing the "immunosuppressive motif" within the envelope protein of human endogenous retrovirus type C. The presence of this peptide was identified only in sera of the patients with chronic myelo- and/or promonocytic leukemia at acute phase. Furthermore, the appearance of this protein correlated with agranulocytosis. SDS-PAGE profile revealed the serum protein recognized by Ab that had MW of 88 kDa. However, in bone marrow cells, the same Ab bound 66 kDa peptide, and low molecular weight peptide, INF-agr;, as well. It was determined that 88 kDa protein was a highly glycosylated version of 66 kDa protein. Staining blood cells and bone marrow cells with FITC-labelled specific monoclonal antibodies demonstrated that CD34(+) cells produced this peptide. The appearance of this peptide in sera of patients with myeloid leukemia was considered as unfavorable prognosis since it was followed with lethality in 50% of cases. Thus, besides potential involvement of endogenous retroviral products in carcinogenesis, they may be considered as a factor of immunosuppression.

A Role of Endogenous Retroviral MCF env Gene in Proliferation of Pluripotent Hemopoietic Progenitors in Mice.

We have investigated the role of endogenous retroviral mink cell focus-forming (MCF) genes in the regulation of mouse bone marrow hemopoietic progenitor cell proliferation. The p15E protein coded by the MCF env gene is expressed by early hemopoietic progenitors, mostly on spleen colony forming units (CFUs-12) and on erythropoietin-independent erythroid progenitors. Stimulation of cell proliferation in hemopoietic precursors by steroid hormone (testosterone propionate) treatment resulted in upregulation of the expression of the endogenous p15E protein on bone marrow cells. Blocking of endogenous retroviral MCF env gene expression on the activated hemopoietic progenitors by antisense oligonucleotides inhibited their proliferation. These data suggest that the endogenous MCF env genes act as growth-regulators for pluripotent hemopoietic progenitors.