Interaction between dendritic cells and natural killer cells during pregnancy in mice.

A complex regulation of innate and adaptive immune responses at the maternal fetal interface promotes tolerance of trophoblast cells carrying paternally derived antigens. Such regulatory functions involve uterine dendritic cells (uDC) and natural killer (uNK) cells. The existence of a NK and DC "cross talk" has been revealed in various experimental settings; its biological significance ranging from cooperative stimulation to cell lysis. Little is known about the presence or role of NK and DC cross talk at the maternal fetal interface. The present study shows that mouse NK and DC interactions are subject to modulation by trophoblast cells in vitro. This interaction promotes a tolerogenic microenvironment characterized by downregulation of the expression of activation markers on uNK cells and uDC and dominance of Th2 cytokines. NK and DC interactions would also influence uterine cell proliferation and this process would be strongly modulated by trophoblast-derived signals. Indeed; while low proliferation rates were observed upon regular coculture allowing direct contact between uterine cells and trophoblasts, incubation in a transwell culture system markedly increased uterine cell proliferation suggesting that soluble factors are key mediators in the molecular "dialog" between the mother and the conceptus during the establishment of mouse pregnancy. Our data further reveal that the regulatory functions of trophoblast cells associated with tolerance induction are impaired in high abortion murine matings. Interestingly, we observed that secretion of interleukin-12p70 by uDC is dramatically abrogated in the presence of uNK cells. Taken together, our results provide the first evidence that a delicate balance of interactions involving NK cells, DC, and trophoblasts at the mouse maternal fetal interface supports a successful pregnancy outcome.

Administration of interferon-alpha in mice provokes peripheral and central modulation of immune cells, accompanied by behavioral effects.

BACKGROUND: Interferon-alpha (IFN-alpha) is used in the treatment of many viral and malignant diseases. Although IFN-alpha administration is highly efficacious, treatment is often complicated by psychiatric side effects such as depression, which may require discontinuation of the therapy. Unfortunately, the mechanisms underlying IFN-alpha-induced depression are still not well understood. METHODS: In this study, we explored behavioral and immune effects of IFN-alpha administration in mice. BALB/c mice received daily intraperitoneal injections of 60,000 U/kg murine IFN-alpha for 8 days. Behavioral and immunological analysis was performed at least 15 h after injection to avoid any acute IFN-alpha effect. We monitored depression and anxiety-like behavior in mice using the Forced Swimming Test (FST), Tail Suspension Test (TST), and Elevated Plus Maze (EPM). Moreover, we studied the expression of adhesion molecules on peripheral blood leukocytes and analyzed the recruitment of lymphocyte subsets into the brain. RESULTS: IFN-alpha administration resulted in increased immobility of mice in the late phase of FST, without significant effects in TST and EPM. Increased percentages of natural killer cells and lymphocytes expressing LFA-1 or Mac-1 were observed in peripheral blood. The percentages of CD4+ and CD8+ lymphocytes as well as the percentages of LFA-1-expressing CD4+ and CD8+ lymphocytes were increased in the brains of IFN-alpha-treated mice. CONCLUSION: Our data suggest that IFN-alpha administration leads to an increase in peripheral blood cells with migratory potential, accompanied by an increased number of lymphocytes in brain, whilst the detectable modulation of the behavior was rather modest.

Comparison of hybrid capture and reverse transcriptase polymerase chain reaction methods in terms of diagnosing human cytomegalovirus infection in patients following hematopoietic stem cell transplantation.

OBJECTIVE: Human cytomegalovirus (CMV) is a life threatening cause of infection among hematopoietic stem cell recipients. Developing reliable methods in detecting the CMV infection is important to identify the patients at risk of CMV infection and disease. The aim of this study was to compare the 2 tests- hybrid capture test, which is routinely used in the diagnosis of CMV infection among hematopoietic stem cell recipients, and reverse transcriptase polymerase chain reaction (RT-PCR) detecting UL21.5 mRNA transcripts of the active virus. METHODS: In this prospective study, a total of 178 blood samples obtained from 35 patients following allogeneic hematopoietic stem cell transplantation at the Bone Marrow Transplantation Unit of the Hematology Department, Ibn-i Sina Hospital of Ankara University School of Medicine, Turkey between January 2003 and September 2003 were analyzed. Hybrid capture and RT-PCR using UL21.5 gene transcript method to investigate HCMV in blood samples were performed at the Department of Microbiology and Clinic Microbiology Ankara University School of Medicine, Turkey. RESULTS: When hybrid capture test was accepted as the golden standard, the sensitivity of RT-PCR was 33%, specificity 100%, false negativity 67%, false positivity 0%, positive predictive value 100%, negative predictive value 74%, and accuracy was 77%. CONCLUSION: Improving this test by quantification, and application of additional gene transcripts, primarily the late gene transcripts can help increase the sensitivity and feasibility.