Apoptotic cell capture by DCs induces unexpectedly robust autologous CD4+ T‐cell responses

Apoptotic cells represent an important source of self‐antigens and their engulfment by dendritic cells (DCs) is usually considered to be related to tolerance induction. We report here an unexpectedly high level of human CD4⁺ T‐cell proliferation induced by autologous DCs loaded with autologous apoptotic cells, due to the activation of more than 10% of naive CD4⁺ T cells. This proliferation is not due to an increase in the costimulatory capacity of DCs, but is dependent on apoptotic cell‐associated material processed through an endo‐lysosomal pathway and presented on DC MHC class II molecules. Autologous CD4⁺ T cells stimulated with apoptotic cell‐loaded DCs exhibit suppressive capacities. However, in the presence of bacterial lipopolysaccharide, apoptotic cell‐loaded DCs induce the generation of IL‐17‐producing cells. Thus, apoptotic cell engulfment by DCs may lead to increased autologous responses, initially generating CD4⁺ T cells with suppressive capacities able to differentiate into Th17 cells in the presence of a bacterial danger signal such as LPS.     

Contribution of perfusion magnetic resonance imaging in a patient with cerebral ganglioglioma

A 48-year-old woman was admitted to the Neurosurgery Department for a large frontal lobe tumor revealed by partial seizures. The patient was conscious and alert. Neurological examination was normal. MRI study showed a right frontal lobe tumor compounded of an anterior solid mass strongly enhanced after gadolinium injection and a posterior voluminous cyst with important mass effect. The cerebral blood volume (CBV) map showed no area of elevated CBV within the tumor consistent with a low-grade tumor. The patient was operated on with a presumed diagnosis of anaplastic oligodendroglioma. Postoperative course was uneventful. Histopathological examination was consistent with a benign ganglioglioma. The patient did not undergo an additional treatment. One year later, the patient was healthy and neurological and neuropsychological examination were normal. MRI study did not show any recurrence. This case emphazises the relevance of perfusion MR imaging in the preoperative workup of glioneuronal and glial tumors.     

Clinical application of functional MRI: a strategic tool for neurosurgery

The purpose was to incorporate preoperative functional imaging data into anatomic data of operative microscope for neurosurgical procedures of patients suffering from lesions contiguous to eloquent brain areas. The day before surgery, patients bearing scalp markers underwent fMRI, just before anatomical contrast-enhanced MR images. FMRI data analysis were realised using a t test (p<0.0001). The resulting functional-anatomical images were downloaded onto a surgical neuronavigation computer in order to outline tumoral target and functional areas. At surgery, cortical stimulation has been used to confirm functional data. Functional image-guided surgery of lesions abutting functional cortex can be safely performed.     

Evidence for the role of ammonia in the intracerebral transfer and metabolism of tryptophan

After portacaval shunt in the rat, the transport of tryptophan and other neutral amino acids across the blood-brain barrier is enhanced. To determine the role of NH3 in the intracerebral transfer of tryptophan and serotonin metabolism, solutions containing either saline or NH3 or tryptophan or NH3 + tryptophan together were infused, respectively, into the internal carotid artery of rats in order to achieve blood levels similar to those observed after liver ischemia. After tryptophan infusion, a significant increase in the hypothalamic levels of tryptophan and 5-hydroxyindoleacetic acid was observed. A similar increment was found after NH3 infusion. NH3 + tryptophan infusion induced a significant increment in hypothalamic tryptophan and 5-hydroxyindoleacetic acid levels which were 2-fold greater than after tryptophan infusion. There was no significant change in 5-hydroxytryptamine levels in any of these experiments. Glutamine levels increased significantly after NH3 infusion. When tryptophan and NH3 were infused simultaneously, a significant reduction in glutamine levels occurred. These results cannot be explained by any modification of cerebral blood flow nor of the cerebral intercellular pH. Our data suggest that NH3 enhances the transfer of tryptophan across the blood-brain barrier and thus stimulates serotonin metabolism. The mechanism by which tryptophan transfer across the blood-brain barrier is facilitated is unknown. The reduction in glutamine levels in the hypothalamus when NH3 and tryptophan are infused together may be explained either by an inhibition of synthesis or by an intercellular influx of neutral amino acids and an efflux of glutamine as suggested by James et al.