LAP+ Treg is a better biomarker than total Treg in viral myocarditis

Latency associated peptide (LAP) is a protein expressed on the membrane of some regulatory T cells (Treg). LAP⁺ Treg have a greater immunomodulatory effect than that of their negative counterparts. In this study, we presented the data on the proportion of LAP⁺ Treg out of CD4⁺ cells in mice with viral myocarditis, which we believed was more sensitive and specific than that of the ratio of total Treg in CD4⁺ cells. Comparing with the previously recognized total Treg, LAP⁺ Treg was a better biomarker on myocardial inflammation.     

Vaccination of sheep with Quil-A® adjuvant expands the antibody repertoire to the Fasciola MF6p/FhHDM-1 antigen and administered together impair the growth and antigen release of flukes

Fasciolosis continues to be a major cause of economic losses in the livestock industry and a growing threat to humans. The limited spectrum of effective anthelmintics and the appearance of resistances urge the need for developing an effective vaccine. Most studies have been focused on the use of TH₁-polarizing adjuvants and the use of recombinant Fasciola critical molecules and, despite the efforts, no reproducible protections have been achieved. The F. hepatica MF6p/FhHDM-1 protein is a heme-binding protein also reported to have immunomodulatory properties, constituting a promising target for vaccination and/or as target for the development of new flukicides. Thus, in this study, we investigated the effects of the TH₁-polarizing adjuvant Quil A® on sheep immune response to MF6p/FhHDM-1, and the vaccine potential of both native and synthetic forms of this protein against ovine fasciolosis. Subcutaneous injection of Quil A® alone, i.e., without co-injecting any antigen, expands the antibody repertoire to MF6p/FhHDM-1 triggered by a subsequent primoinfection with metacercariae. This effect was not observed with aluminum hydroxide, the most frequently adjuvant used in commercial vaccines. On the other hand, vaccination with synthetic MF6p/FhHDM-1 in Quil A® prompted a 2–4-week delay in the antibody response induced in sheep by a challenge experimental infection. Moreover, fluke populations stablished showed stunted growth and low antigen release probably due to reduced metabolic activity. These observations suggest that primary circulating antibodies induced by the immunization had harmful effects on fluke development. Such effects could not be demonstrated to be associated to TH₁ immune response linked events (production of IgG₂ isotype antibodies and IFN-γ).     

Helios,and not FoxP3, is the marker of activated Tregs expressing GARP/LAP

Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4⁺FoxP3⁻ T cells expressing Helios (FoxP3⁻Helios⁺) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4⁺Helios⁺ T cells regardless of FoxP3 expression (FoxP3^+/−Helios⁺). We show that CD4⁺GARP^+/−LAP⁺ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3⁺Helios⁺ Tregs proliferate in vitro significantly less than FoxP3⁺Helios⁻ Tregs upon TCR stimulation. Unlike FoxP3⁺Helios⁻ Tregs, FoxP3⁺Helios⁺ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3⁺Helios⁺ Tregs have more suppressive characteristics, compared with FoxP3⁺Helios⁻ Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3⁺Helios⁺ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.     

An electrophysiological investigation of discourse coherence in healthy adults

This study used event-related potentials (ERPs) to investigate discourse-coherence processing. Because there are scant data on ERP indices of discourse coherence in typical adults, it is important to study a non-clinical population before examining clinical populations. Twelve adults listened to a story with sentences in a coherent versus incoherent order. Sequences of nonsense syllables served as a control. ERPs in the 200–400?ms time window, reflecting phonological and lexical processing, and in the 600–900?ms time window, reflecting later discourse processing for integration, were investigated. Results revealed a right anterior and posterior positivity that was greater for coherent than for incoherent discourse during the 600–900?ms time window. These findings point to an index of discourse coherence and further suggest that ERPs can be used as a clinical tool to study discourse-processing disorders in populations with brain damage, such as aphasia and traumatic brain injury.