No abstract

Reported alterations in T(reg) cells from type 1 diabetes (T1D) patients led us to a revision of their phenotypical features compared with controls. A fine cytometric analysis was designed for their characterization, using a panel of markers including FOXP3, CTLA4, glucocorticoid-induced TNFR family related (GITR) and CD127. The frequency of peripheral CD4(+)CD25(hi) T(reg) cells was similar between samples. However, the yield of sorted T(reg) cells was significantly lower in patients than in controls. When comparing the T(reg)-cell phenotype between samples, the only difference concerned the expression of GITR. A significant decrease of GITR(+) cells and GITR mean fluorescence intensity within the T(reg)-cell population, and to a lesser extent in the effector population, was observed in T1D compared with controls. Moreover, GITR expression was analyzed in several conditions of T-cell activation and differences were only observed in T1D T(reg) cells versus controls when responding to sub-optimal stimulation, that is, soluble anti-CD3 or medium alone but not in the presence of anti-CD3-/anti-CD28-coated beads. However, expanded T1D T(reg)-cell-mediated suppression was as efficient as that mediated by their control counterparts, showing no association between their regulatory capacity and the reduced GITR. Our results show a higher susceptibility to apoptosis in patients' versus controls' T(reg) cells, suggesting that GITR is a T(reg)-cell marker that would be primarily involved in T(reg)-cell survival rather than in their suppressor function.

Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.

Highlights d Human and rat CD8 + Tregs recognize long peptides derived from donor MHC class II molecules d A cross-reactive CD8 + Treg population recognizes different MHC class II-derived peptides d In vivo tolerogenic peptide vaccination induces CD8 + Tregs and transplantation tolerance