Alemtuzumab is a humanized anti-CD52 mAb that has emerged as a safe and effective lymphocyte-depleting agent for induction therapy in renal transplantation. Recent reports have suggested that acute cellular rejection (ACR) of renal allografts in patients who receive alemtuzumab induction may be mediated by an atypical population of monocytes and not through "classical" T cell-dependent pathways of allorecognition. However, more recently, T cells with memory phenotype have been described in renal biopsies that were taken from alemtuzumab-treated patients who were experiencing ACR. This study investigated the cellular basis of ACR after alemtuzumab induction as compared with ACR that was associated with nondepleting therapy. Twelve biopsies from patients who were treated with a single dose of alemtuzumab at the time of transplantation and subsequently developed ACR were stained for the following cell markers: CD3 (T cells), CD68 (monocytes), CD20 (B cells), and CD45RO and CD45RA (memory and naïve T cells). ACR biopsies from six patients who received no induction therapy were used as controls. In alemtuzumab-treated patients, ACR occurred despite profound lymphopenia.
We examined potential benefits of group living in juvenile lake sturgeon (Acipenser fulvescens Rafinesque, 1817) and whether those benefits applied equally to associations with conspecific and allospecific individuals. In the first experiment, one focal lake sturgeon was placed with either seven size-matched conspecifics, allospecifics, or in isolation and given a 30 s air exposure. In the second experiment, one focal lake sturgeon was placed with either seven conspecifics or in isolation and was exposed to a conspecific skin homogenate as a potential alarm substance or a control of distilled water. Cortisol, norepinephrine, and epinephrine levels were measured before and after exposure in each experiment via an indwelling cannula in the caudal sinus. In the first experiment, lake sturgeon held with allospecifics and in isolation had a significantly longer norepinephrine response. Furthermore, plasma norepinephrine concentration in the focal lake sturgeon in the allospecific treatment was significantly higher than the other treatments following air exposure. In the second experiment, there was no behavioural or hormonal response to the introduction of conspecific skin homogenate, yet isolated fish had elevated baseline norepinephrine and cortisol levels. Finally, comparison of baseline levels of all three hormones between two ages of juveniles indicated an effect of age on baseline epinephrine levels. Our findings confirm the potential physiological benefit of group living in lake sturgeon and suggest an ontogenetic shift in both the behavioural response to potential stressors and the baseline hormonal levels that may influence fitness.
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