Biomedical subjects
U Mahlknecht
Publications and source records attributed to U Mahlknecht.
Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4.
CD8-positive T cells are thought to play an important role in the control of infection by human immunodeficiency virus (HIV) as a result of their cytotoxic activity and by releasing soluble factors. In AIDS patients, the absolute number of CD8+ T lymphocytes is decreased in peripheral blood and their turnover rate is increased, suggesting that there is more cell renewal and cell death occurring. Anti-retroviral therapy raises CD8+ T-cell counts in HIV-infected patients. Here we report that the death rate of CD8+ T cells by apoptosis increased markedly during HIV infection of peripheral blood mononuclear cells in vitro. Apoptosis is induced in a dose-dependent manner by recombinant envelope glycoprotein gp120 from HIV strain X4, or by stromal-derived factor-1 (SDF-1), the physiological ligand of the chemokine receptor CXCR4. Apoptosis is mediated by the interaction between tumour-necrosis factor-alpha bound to the membrane of macrophages (mbTNF) and a receptor on CD8+ T cells (TNF-receptor II, or TNFRII). The expression of both of these cell-surface proteins is upregulated by HIV infection or by treatment with recombinant gp120 or SDF-1. Apoptosis of CD8+ T cells isolated from HIV-infected patients is also mediated by macrophages through the interaction between mbTNF and TNFRII. These results indicate that the increased turnover of CD8+ T cells in HIV-infected subjects is mediated by the HIV envelope protein through the CXCR4 chemokine receptor.
Successful treatment of disseminated central nervous aspergillosis in a patient with acute myeloblastic leukemia.
Invasive opportunistic mycoses are common complications in patients suffering from hematological disorders. Brain abscesses in the immunocompromised host are known to be most frequently caused by fungi of the Aspergillus species and are often associated with concomitant pulmonary disease. As the penetration of the currently available antifungal agents into the brain tissue is limited, only very few patients have been described to survive this life-threatening condition. We report the case of a 62 year old female patient who presented with multiple aspergillus brain abscesses during prolonged neutropenia following induction chemotherapy for acute myeloblastic leukemia and was successfully treated with high dose (8 mg/kg/day) liposomal amphotericin B.
The toxic shock syndrome toxin-1 induces anergy in human T cells in vivo.
TSST-1 is a Staphylococcus aureus-derived superantigen which has been implicated in the pathogenesis of toxic shock syndrome. In mice, superantigen-induced proliferation is followed by deletion or anergy of reactive T cells. So far, superantigen-induced T-cell anergy has not been observed in humans. We therefore examined PBMCs derived from a 15-year-old patient suffering from severe toxic shock syndrome. Markedly elevated levels of circulating TSST-1-reactive T cells were found by cytofluorometric analysis. Upon in vitro restimulation with TSST-1, hyporesponsiveness of TSST-1-responsive V beta 2+ T cells was detected, thus confirming results obtained in the murine system.
Activation of human T cells by the superantigen Staphylococcus enterotoxin B: analysis on a cellular level.
Superantigens interact with and activate a sizeable fraction of T cells characterized by expression of specific V beta gene segments of their antigen receptor. The massive activation of T cells in an organism is considered responsible for clinical symptoms associated with superantigen-producing bacteria. Here we studied the in vitro activation of human T cells by the superantigen Staphylococcus Enterotoxin B on a cell by cell basis. Superantigen-reactive T cells were stained with a V beta 12-specific monoclonal antibody and analyzed in a cytofluorograph. Blast formation of SEB-reactive T cells occurs within 12 h and reaches a plateau after 24 h. Double-staining of V beta 12+ T cells with antibodies against different T cell activation or adhesion surface molecules revealed a time-dependent differential upregulation for CD2, CD11 = LFA-1, CD25, CD28, CD69, and HLA-DR. The expression of CD3, CD4 and CD5 was not influenced by the superantigen. The rapid phenotypic changes of superantigen reactive T cells in terms of marker expression and cell size could provide early tools in diagnosing diseases caused by superantigens.