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Reduced stratum corneum hydration correlates with pruritus in patients on maintenance haemodialysis and peritoneal dialysis, and may be alleviated by simple emollient therapy.

In patients infected with multidrug-resistant HIV, structured interruption of treatment was associated with greater progression of disease and did not confer immunologic or virologic benefits or improve the overall quality of life.

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A perforating disorder of the skin developing in association with chronic renal failure and often also diabetes, acquired perforating dermatosis (APD), affects up to 10% of patients receiving maintenance haemodialysis in North America. The prevalence of this condition in British dialysis patients has not yet been ascertained. We have undertaken a skin survey of our dialysis population (n = 80) to determine the prevalence and clinical presentation of APD, with subsequent assessment of disease management and outcome. Of 72 patients who participated in the survey, eight were found to have APD, seven of whom were also diabetic. Skin lesions had developed pre-dialysis in two patients, on commencement of dialysis in one, and after 1-3 years on dialysis in the remaining five. Patients typically presented with pruritic dome-shaped papules with central crusts arising on the trunk and extensor limb surfaces. Histological examination of biopsy specimens revealed two types of lesion, typified by either narrow or broad ulcer craters, each showing perforation of both collagen and elastic fibres. Topical/intradermal steroid or topical retinoid were effective therapies in certain of our patients. Clinical clearance was achieved after 3-12 months of treatment in five patients with improvement in the remaining two patients who received treatment. Of the four patients who were alive at 2-year review, three remained clear, while one patient continued to develop new lesions. We report an 11% prevalence of APD in our dialysis population, suggesting the disorder to be as prevalent in patients with chronic renal failure in Britain as in North America. An association of the disorder with long-standing diabetes was confirmed.

While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are still poorly defined. We find that following murine influenza infection, most effector CD4 T cells undergo apoptosis unless they encounter cognate Ag at a defined stage near the peak of effector generation. Ag recognition at this “memory checkpoint” blocks default apoptosis and programs their transition to long-lived memory. Strikingly, we find that viral infection is not required, as memory formation can be restored by the addition of short-lived, Ag-pulsed APC at this checkpoint. The resulting memory CD4 T cells express an enhanced memory phenotype, have increased cytokine production, and provide protection against lethal influenza infection. Finally, we find that memory CD4 T cell formation following cold-adapted influenza vaccination is boosted when Ag is administered during this checkpoint. These findings imply that persistence of viral Ag presentation into the effector phase is the key factor that determines the efficiency of memory generation. We also suggest that administering Ag at this checkpoint may improve vaccine efficacy.

The migration of mature dendritic cells (DCs) into the draining lymph node (dLN) is thought to depend solely on the chemokine receptor CCR7. CD301b DCs migrate into the dLN after cutaneous allergen exposure and are required for T helper 2 (Th2) differentiation. We found that CD301b DCs poorly upregulated CCR7 expression after allergen exposure and required a second chemokine signal, mediated by CCR8 on CD301b DCs and its ligand CCL8, to exit the subcapsular sinus (SCS) and enter the lymph node (LN) parenchyma. After allergen exposure, CD169SIGN-R1 macrophages in interfollicular regions produced CCL8, which synergized with CCL21 in a Src-kinase-dependent manner to promote CD301b DC migration. In CCR8-deficient mice, CD301b DCs remained in the SCS and were unable to enter the LN parenchyma, resulting in defective Th2 differentiation. We have defined a CCR8-dependent stepwise mechanism of DC-subset-specific migration through which LN CD169SIGN-R1 macrophages control the polarization of the adaptive immune response.