Migration of V delta 1 and V delta 2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1-infected patients: competition by HIV-1 Tat

We show that HIV-1-infected patients have increased concentrations of circulating V delta 1 T cells (2.2%-9.0% of T lymphocytes; healthy donors, 1.0%-2%) and, in some instances, V delta 2 T cells (3.5%-4.8% vs 2.0%-3.3%). In these patients, both V delta 1 and V delta 2 T cells are CXCR3+CXCR4+, whereas in healthy donors CXCR4 was preferentially expressed on V delta 1 T lymphocytes. gamma delta T cells transmigrated across endothelial monolayers, in response to interferon-gamma-inducing protein-10 (IP-10/CXCL10), stromal cell-derived factor-1 (SDF-1/CXCL12), or both, according to the expression of the specific receptors CXCR3 and CXCR4. Interestingly, 6Ckine/SLC/CCL21 was more effective than IP-10/CXCL10 on V delta 1 CXCR3+ cells, whereas V delta 2 CXCR3+ cells were driven more efficiently by IP-10/CXCL10. IP-10/CXCL10- and SDF-1/CXCL12-induced transmigration was dependent on phosphoinositide-3 kinase (PI-3K), as demonstrated by the use of the specific blockers wortmannin and LY294002 and by the activation of the downstream serine kinase Akt/PKB on ligation of CXCR3 and CXCR4. Occupancy of CXCR3, but not of CXCR4, led to CAMKII activation; accordingly, the CAMKII inhibitors KN62 and KN93 decreased IP-10/CXCL10- but not SDF-1/CXCL12-driven transmigration. Finally, HIV-1 Tat, which is present in the serum of HIV-1-infected patients, interferes with the chemotactic activity of these chemokines because of the cysteine-rich domain of the protein, which contains CXC and CC chemokine-like sequences.     

A new model of epidermal culture for the surgical treatment of vitiligo

Background Vitiligo can be successfully treated with grafts of autologous cultured epidermal cells. Objective To evaluate the efficacy of autologous grafting of epidermal cells, cultured by an original method, in the treatment of localized vitiligo refractory to other therapies. Methods Autologous normally pigmented skin was used to culture keratinocytes and melanocytes on a supporting layer of biomaterial (Laserskin), which was grafted directly onto achromatic skin after de-epithelialization with liquid carbon dioxide. The percentage area of repigmentation was calculated by image analysis. Results Initial repigmentation of the treated areas was observed 1 month after treatment. Repigmentation continued to increase for 3 months after grafting. Follow-up at 3, 6, 12, and 18 months showed almost complete repigmentation in six out of 11 cases. In four other patients, 40–71% of the grafted achromatic area was repigmented. In one patient, repigmentation was impeded by sepsis. Conclusions The method was found to be effective in the treatment of localized vitiligo refractory to other treatments. The therapeutic procedure was simple, reproducible, and easy to use.     

Innovative immunosuppression in kidney transplantation: A challenge for unmet needs

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries, new innovative drugs in kidney transplantation are difficult to be encountered. The best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the market. These unmet needs are the prevention of delayed graft function (DGF), the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated rejection. These needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible grafts. The first are particularly exposed to DGF, the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often occur. Particular caution is needed in treating these drugs. First, they are described in very recent studies and the follow-up of their effect is of course rather short. Second, some of these drugs are still in an early phase of study, even if in well-conducted randomized controlled trials. Particular caution and a careful check need to be used in trials launched 2 or 3 years ago. Indeed, is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.     

Modulation of immune response to group C meningococcal conjugate vaccine given intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl chitosan delivery system

Previous work had shown that the immunogenicity of conjugate vaccine against group C meningococci (CRM-MenC) is enhanced when it is delivered intranasally (inl) with mucosal adjuvants, such as mutants of the Escherichia coli enterotoxin (LT), and with delivery systems such as chitosan derivatives. We show, in mice, that the concomitant use of limiting doses of the fully nontoxic LTK63 mutant as a mucosal adjuvant and of the trimethyl derivative of chitosan as a delivery system allows the reduction of each of the components for the induction of antibody and bactericidal responses to CRM-MenC conjugate vaccine delivered inl at titers similar to or higher than those induced by parenteral immunization. These data could affect the design of efficacious mucosal vaccines and their safety.     

Rapid regression of psoriasis in a coeliac patient after gluten-free diet. A case report and review of the literature

BACKGROUND: Several skin disorders are present in patients affected by coeliac disease (CD) - among them, psoriasis has been described. However, at present the relationship between CD and psoriasis remains controversial since there are few and contrasting data on this topic. METHOD: Here we describe a case of psoriasis in a CD patient not responding to specific therapies for psoriasis. RESULT: The regression of skin lesions after gluten-free diet (GFD) was evident in a short time. CONCLUSION: The present case supports the association between CD and psoriasis and the concept that psoriasis in CD patients can be improved by GFD. Future studies are needed to clarify the possible mechanisms involved in this association.     

Segmental dyskinesia in Wolff-Parkinson-White syndrome: a possible cause of dilatative cardiomyopathy

Wolff-Parkinson-White (WPW) is a syndrome characterized by the presence of an accessory pathway that skipping A-V node may lead the electrical stimulus from the atrium directly to the ventricle. Some studies reported the finding of myocardial dyskinesia in the segments precociously activated by the accessory pathway, at echocardiogram and at nuclear cardiac study. Soria et al. reported, in 1985, an increased incidence of dilative cardiomyopathy in patients with WPW. The pathophysiological pathway that leads to ventricular dilation may be due to the increase of end-diastolic pressure secondary to a tachycardia-induced cardiomyopathy. Tachycardia-induced cardiomyopathy is usually secondary to frequent and prolonged tachycardia episodes. In this paper we report the cases of three patients affected by WPW who developed dilative cardiomyopathy during the follow-up. Particularly dyskinetic segments, working such as a functional aneurysm, could induce deep modifications of intraventricular haemodynamics, leading to remodelling and progressive ventricular dilation. This hypothesis could have important empirical consequences because it could imply the necessity of a precocious ablative therapy in this kind of patients.     

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

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