[Polycythaemia in a patient with uterus myomatosus]. / Polycytemie bij een patiënte met een uterusmyoom.

BACKGROUND: Myomatous erythrocytosis syndrome (MES) is characterised by a combination of polycythaemia, uterus myomatosus and the normalisation of erythrocyte count after hysterectomy. CASE DESCRIPTION: A 58-year-old postmenopausal woman was referred to the gynaecologist with symptoms of vaginal blood loss, increased abdominal circumference and pollakiuria. Physical examination indicated her uterus was enlarged to the size of a 24-week gestation. Endometrial malignancy was excluded and ultrasound showed a myoma. In consultation with the patient a hysterectomy was planned. Pre-operative blood tests showed increased haemoglobin levels (14.2 mmol/l). No indications of polycythaemia vera or secondary polycythaemia were found after which the diagnosis of MES was made. Haemoglobin levels normalised after hysterectomy without any further intervention. CONCLUSION: MES is common, although relatively unknown. Its pathophysiology is most likely based on ectopic production of erythropoietin by leiomyoma tissue. The combination of polycythaemia and uterus myomatosus should alert clinicians to this syndrome, especially as polycythaemia normalises after hysterectomy.

Cognate CD4 T-cell licensing of dendritic cells heralds anti-cytomegalovirus CD8 T-cell immunity after human allogeneic umbilical cord blood transplantation.

UNLABELLED: Reactivation of human cytomegalovirus (CMV) is hazardous to patients undergoing allogeneic cord blood transplantation (CBT), lowering survival rates by approximately 25%. While antiviral treatment ameliorates viremia, complete viral control requires CD8+ T-cell-driven immunity. Mouse studies suggest that cognate antigen-specific CD4+ T-cell licensing of dendritic cells (DCs) is required to generate effective CD8+ T-cell responses. For humans, this was not fully understood. We here show that CD4+ T cells are essential for licensing of human DCs to generate effector and memory CD8+ T-cell immunity against CMV in CBT patients. First, we show in CBT recipients that clonal expansion of CMV-pp65-specific CD4+ T cells precedes the rise in CMV-pp65-specific CD8+ T cells. Second, the elicitation of CMV-pp65-specific CD8+ T cells from rare naive precursors in cord blood requires DC licensing by cognate CMV-pp65-specific CD4+ T cells. Finally, also CD8+ T-cell memory responses require CD4+ T-cell-mediated licensing of DCs in our system, by secretion of gamma interferon (IFN-γ) by pp65-specific CD4+ T cells. Together, these data show that human DCs require licensing by cognate antigen-specific CD4+ T cells to elicit effective CD8+ T-cell-mediated immunity and fight off viral reactivation in CBT patients. IMPORTANCE: Survival rates after stem cell transplantation are lowered by 25% when patients undergo reactivation of cytomegalovirus (CMV) that they harbor. Immune protection against CMV is mostly executed by white blood cells called killer T cells. We here show that for generation of optimally protective killer T-cell responses that respond to CMV, the early elicitation of help from a second branch of CMV-directed T cells, called helper T cells, is required.

Antigen cross-presentation: extending recent laboratory findings to therapeutic intervention.

The initiation of adaptive immune responses requires antigen presentation to lymphocytes. In particular, dendritic cells (DCs) are equipped with specialized machinery that promote effective display of peptide/major histocompatibility complexes (MHC), rendering them the most potent stimulators of naive T lymphocytes. Antigen cross-presentation to CD8(+) T cells is an important mechanism for the development of specific cytotoxic T lymphocyte (CTL) responses against tumours and viruses that do not infect antigen-presenting cells. Here, we review recent findings concerning antigen cross-presentation to CD8(+) T lymphocytes. Specific subtypes of DCs in the mouse have been defined as being especially endowed for antigen cross-presentation, and a human homologue of these DCs has recently been described. DC vaccination strategies for the prevention and treatment of human diseases have been under investigation in recent years, but have not generally reached satisfying results. We here provide an overview of new findings in antigen cross-presentation research and how they can be used for development of the next generation of human DC vaccines.

[Revised guideline 'prevention of cot death']. / Herziene richtlijn 'preventie wiegendood'.

There are new insights into the pathogenesis of cot death ('sudden infant death syndrome'; SIDS). Based on these new insights, the Dutch Paediatric Association and the Dutch Child and Youth Health Care Physicians have drawn up a new guideline 'Prevention of cot death', which replaces the consensus statement of 1996. The 2 major differences from the old guideline are that co-sleeping of young infants in the same bed with the parents is now actively discouraged under the age of 4 months, and that the supine sleeping position is recommended from birth on. The recommendation that lying on one side can be used during the first 2 weeks of life has now been withdrawn.