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Antonio Almeida

Publications and source records attributed to Antonio Almeida.

6 recordsLinked to original sources
PubMed2005

Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells.

Invariant natural killer T cells (iNKT cells) are a small subset of immunoregulatory T cells highly conserved in humans and mice. On activation by glycolipids presented by the MHC-like molecule CD1d, iNKT cells promptly secrete T helper 1 and 2 (Th1/2) cytokines but also cytokines with hematopoietic potential such as GM-CSF. Here, we show that the myeloid clonogenic potential of human hematopoietic progenitors is increased in the presence of glycolipid-activated, GM-CSF-secreting NKT cells; conversely, short- and long-term progenitor activity is decreased in the absence of NKT cells, implying regulation of hematopoiesis in both the presence and the absence of immune activation. In accordance with these findings, iNKT-cell-deficient mice display impaired hematopoiesis characterized by peripheral-blood cytopenias, reduced marrow cellularity, lower frequency of hematopoietic stem cells (HSCs), and reduced early and late hematopoietic progenitors. We also show that CD1d is expressed on human HSCs. CD1d-expressing HSCs display short- and long-term clonogenic potential and can present the glycolipid alpha-galactosylceramide to iNKT cells. Thus, iNKT cells emerge as the first subset of regulatory T cells that are required for effective hematopoiesis in both steady-state conditions and under conditions of immune activation.

Animals↗
PubMed2005

Human invariant NKT cells are required for effective in vitro alloresponses.

NKT cells are a small subset of regulatory T cells conserved in humans and mice. In humans they express the Valpha24Jalpha18 invariant chain (hence invariant NKT (iNKT) cells) and are restricted by the glycolipid-presenting molecule CD1d. In mice, iNKT cells may enhance or inhibit anti-infectious and antitumor T cell responses but suppress autoimmune and alloreactive responses. We postulated that iNKT cells might also modulate human alloreactive responses. Using MLR assays we demonstrate that in the presence of the CD1d-presented glycolipid alpha-galactosylceramide (alphaGC) alloreactivity is enhanced (37 +/- 12%; p < 0.001) in an iNKT cell-dependent manner. iNKT cells are activated early during the course of the MLR, presumably by natural ligands. In MLR performed without exogenous ligands, depletion of iNKT cells significantly diminished the alloresponse in terms of proliferation (58.8 +/- 24%; p < 0.001) and IFN-gamma secretion (43.2 +/- 15.2%; p < 0.001). Importantly, adding back fresh iNKT cells restored the reactivity of iNKT cell-depleted MLR to near baseline levels. CD1d-blocking mAbs equally reduced the reactivity of the iNKT cell-replete and -depleted MLR compared with IgG control, indicating that the effect of iNKT cells in the in vitro alloresponse is CD1d-dependent. These findings suggest that human iNKT cells, although not essential for its development, can enhance the alloreactive response.

Antigens, CD1↗
PubMed2005

Bone involvement in sickle cell disease.

Bone involvement is the commonest clinical manifestation of sickle cell disease both in the acute setting such as painful vaso-occlusive crises, and as a source of chronic, progressive disability such as avascular necrosis. Management of these problems is often difficult because of the diagnostic imprecision of most laboratory and imaging investigations and because of the lack of evidence for most surgical procedures in sickle cell disease. This review first discusses the acute problems related to bone involvement in sickle cell disease, with particular reference to differentiating infection from infarction, and then describes the long-term effects of sickle cell disease on bone mineral density, growth, and chronic bone and joint damage.

Acute Disease↗
PubMed2003

Thromboprophylaxis with unmonitored intermediate-dose low molecular weight heparin in pregnancies with a previous arterial or venous thrombotic event.

The comparatively high rate of complications, both to the mother and foetus, of warfarin and unfractionated heparin have led to an increased use of low molecular weight heparins (LMWH) in pregnant women at risk of thrombosis. However, despite reliable pharmacokinetics of LMWH, current practice is that anti-activated factor X levels are monitored in this group of patients. We report the use of unmonitored dalteparin in 27 pregnancies of 25 women who had previous thrombotic events. All women had normal renal function and weighed less than 85 kg prior to conceiving. The regimen consisted of 5000 IU dalteparin once daily started at the time of a positive pregnancy test, and increased to twice daily at 16-20 weeks gestation. In this cohort of patients there was a low complication rate. None of the women developed recurrent venous thromboses during these pregnancies but two women with known cerebral antiphospholipid syndrome developed recurrent cerebral ischaemia, which responded to an increase in dose. In our small group of patients, we have found that the use of intermediate-dose LMWH in pregnant women does not need to be monitored, and that it is safe and probably effective in preventing recurrent venous but not arterial thromboembolic events in high-risk pregnancies.

Adult↗