A5084277682- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Drug-Induced Hepatotoxicity and Protection
- HIV/AIDS Research and Interventions
- Liver Diseases and Immunity
- Immunodeficiency and Autoimmune Disorders
- Cytomegalovirus and herpesvirus research
- HIV/AIDS drug development and treatment
- Drug Transport and Resistance Mechanisms
- Microscopic Colitis
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Hepatitis C virus research
- Drug-Induced Adverse Reactions
- Inflammatory Bowel Disease
- Liver Disease Diagnosis and Treatment
- Neuropeptides and Animal Physiology
- Hepatitis B Virus Studies
- Diabetes and associated disorders
- Blood disorders and treatments
- Eosinophilic Disorders and Syndromes
- HIV-related health complications and treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Autoimmune and Inflammatory Disorders
Hospital de Santa Maria
2011-2020
University of Lisbon
2010-2019
Centro Hospitalar Lisboa Norte
2010-2019
Instituto de Medicina Molecular João Lobo Antunes
2006-2019
Institute of Occupational Medicine
2016
Instituto de Medicina Tropical
2012-2013
Hospital de Clínicas
2008
London Postgraduate Medical and Dental Education
1979-1981
University of Ulster
1981
Royal Victoria Hospital
1981
Abstract The causal relationships among CD4 cell depletion, HIV replication, and immune activation are not well understood. HIV-2 infection, “nature’s experiment” with inherently attenuated disease, provides additional insights into this issue. We report the finding that in HIV-1 patients a comparable degree of depletion imbalance relative sizes naive memory T populations up-regulation CD8 markers (HLA-DR, CD38, CD69, Fas molecules) similar, even though viral load plasma HIV-2-infected is...
The objective of this study is to present and validate a clinical scale for the diagnosis drug-induced liver injury (DILI). Five components were selected be included in scale: temporal relationship between drug intake onset picture, exclusion alternative causes, extrahepatic manifestations, rechallenge or accidental re-exposure, previous report medical literature. relative importance each component was weighed, arbitrary scores attributed. probability DILI expressed as final score, which...
Background —Diagnosis of drug induced liver injury is usually based on a temporal relation between intake and clinical picture as well the exclusion alternative causes. More precise diagnosis has been attempted by using in vitro specific T cell reactivity to drugs but test never reached general acceptability because frequent negative results which could be explained, part, prostaglandin producing suppressor cells (PPSC). Aim —To analyse diagnostic value modified where lymphocyte responses...
IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation the circulating follicular helper subset was recently shown to be enriched Th17 able help differentiation. We investigated putative link between Th17-cell homeostasis B by studying compartment primary immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined defects into...
Summary Background Venom immunotherapy (VIT) induces long‐lasting immune tolerance to hymenoptera venom antigens, but the underlying mechanisms are not yet clarified. Regulatory T cells thought play an important role in allergic diseases and induction during specific immunotherapy. Aim Characterize longitudinally impact of VIT on pool circulating regulatory cells. Methods Fourteen venom‐allergic patients with severe reactions (grades III–IV) were studied before, 6 12 months after starting...
Common variable immunodeficiency disorders (CVID), the most frequent cause of symptomatic primary immunodeficiency, are defined by impaired antibody production. Notwithstanding, T cell activation and granulomatous manifestations represent main causes CVID morbidity even in patients receiving immunoglobulin (Ig) G replacement therapy. Additionally, gut pathology is a feature CVID. In this study, we investigated monocyte imbalances their possible relationship with increased microbial...
Naïve FoxP3-expressing regulatory T-cells (Tregs) are essential to control immune responses via continuous replenishment of the activated-Treg pool with thymus-committed suppressor cells. The mechanisms underlying naïve-Treg maintenance throughout life in face age-associated thymic involution remain unclear. We found that adults thymectomized early infancy is remarkably well preserved, contrast conventional naïve CD4 T-cells. Naïve-Tregs featured high levels cycling and pro-survival markers,...
Hepatic injury in association with naproxen therapy is described and documented by liver biopsy one patient. Histological findings were consistent a drug-induced hepatitis, cessation of led to reversal the clinical biochemical changes. Circumstantial evidence favour hypersensitivity response drug rather than direct hepatotoxicity. Increased awareness clinicians this probably rare side effect may help prompt identification similar cases.
Viremia is significantly lower in HIV-2 than HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1(+)) and HIV-2(+) individuals, matched CD4 T cell depletion, exhibited gag mRNA levels, indicating significant transcription occurring...
Naive CD4 T-cell maintenance is critical for immune competence. We investigated here the fine-tuning of homeostatic mechanisms naive compartment to counteract loss de novo generation. Adults thymectomized in early childhood during corrective cardiac surgery were grouped based on presence or absence thymopoiesis and compared with age-matched controls. found that preservation CD31- subset was independent thymus its size tightly controlled by peripheral mechanisms, including prolonged cell...
Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis pan-immune activation associated with disease progression. Although having same clinical spectrum, HIV-2 infection characterized by a strikingly lower viremia much slower rate CD4 decline AIDS...
Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation patient with rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers aberrant double-negative αβ T-cells (CD4negCD8neg, DN) regulatory-like T-cells. These data raise the possibility that rudiment persisted, allowing T-cell development,...
Human immunodeficiency virus (HIV) type 2 infection is associated with a better clinical outcome, slower rates of CD4 T cell decline, and lower viremia than HIV-1. This study compares HIV-1 HIV-2 in regard to the percentages interleukin (IL)–2–, interferon (IFN)–γ–, IL-4–producing cells at single-cell level, as determined by flow cytometry. At given degree depletion, frequency able produce IL-2 preserved infection, particularly within subset. As described for immunodeficiency, HIV-2–positive...
Haploidentical hematopoietic stem cell transplantation (HSCT) constitutes an important alternative for patients lacking a human leukocyte antigen (HLA)-matched donor. Although the use of haploidentical donors is increasingly common, long-term impact generating donor-derived immune system in context HLA-mismatched thymic environment remains poorly characterized. We performed in-depth assessment reconstitution group HSCT recipients 4 to 6 years posttransplantation, parallel with respective...
Abstract FOXP3-expressing regulatory T cells (Treg) are essential for the prevention of autoimmunity and were shown to be reduced and/or dysfunctional in several autoimmune diseases. Although Treg-based adoptive transfer represents a promising therapy, large cell number required achieve clinical efficacy constitutes an important limitation. Therefore, novel strategies generate bona fide vitro–induced Treg (iTreg) critical. In this study, we report that human memory CD4 can efficiently...
Abstract The effects of highly active antiretroviral therapy on cytokine imbalances associated with HIV-1 infection have not been characterized. Using single cell analysis by flow cytometry, we show that a significant recovery in the frequency IL-2-producing cells was only observed patients sustained control viral replication and overexpanded CD8 T population CD28− IFN-γ+ significantly reduced after 1 yr effective therapy. Moreover, detrimental role IL-4 is suggested association between an...
ABSTRACT CCR5 expression determines susceptibility to infection, cell tropism, and the rate of human immunodeficiency virus type 1 (HIV-1) disease progression. is also considered major HIV-2 coreceptor in vivo, spite broad use vitro. Here we report a significantly increased proportion memory-effector CD4 T cells expressing HIV-2-infected patients correlating with depletion. Moreover, proviral DNA was essentially restricted CD4, suggesting that this main target for HIV-2. Similar levels were...
IL-7 is a nonredundant cytokine for T cell homeostasis. Circulating levels increase in lymphopenic clinical settings, including HIV-1 infection. HIV-2 infection considered "natural" model of attenuated HIV disease given its much slower rate CD4 decline than and limited impact on the survival majority infected adults. We compared untreated HIV-1- HIV-2-infected patients found that cohort demonstrated delayed during progressive depletion circulating cells as well dissociation between...
Venom-specific immunotherapy (VIT) is well recognized by its efficacy, and compelling evidence implicates regulatory T cells (Tregs) in the underlying tolerogenic mechanisms. Additionally, hymenoptera venom has for a long time been claimed to modulate immunity. Here, we investigated putative role of bee (Bv) human FOXP3-expressing Treg homeostasis differentiation, irrespective donors' allergic status. We found that Bv significantly enhanced differentiation both from conventional naïve CD4...
A severe and prolonged form of biopsy-proved cholestatic hepatitis occurred in a 45-year-old man who had received floxacillin for two weeks preceding the episode drug-related injury. Immunologic tests revealed evidence vitro sensitization to drug as well serum normal subject collected after ingestion floxacillin. Floxacillin should be added list drugs causing hepatitis, most likely by an immunologic mechanism.