- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Rheumatoid Arthritis Research and Therapies
- Diabetes and associated disorders
- Cytokine Signaling Pathways and Interactions
- Fibromyalgia and Chronic Fatigue Syndrome Research
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- IL-33, ST2, and ILC Pathways
- Renal Transplantation Outcomes and Treatments
- Long-Term Effects of COVID-19
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- Hematopoietic Stem Cell Transplantation
- Mesenchymal stem cell research
- Asthma and respiratory diseases
- Lymphoma Diagnosis and Treatment
- Reproductive System and Pregnancy
- Immune Response and Inflammation
- Autoimmune and Inflammatory Disorders Research
University of Coimbra
2010-2025
University of Lisbon
2015-2024
Instituto Gulbenkian de Ciência
2013-2024
Hospital de Egas Moniz
2010-2023
Instituto de Medicina Molecular João Lobo Antunes
2011-2022
Lusíada University of Lisbon
2018
University of Oxford
2000-2006
Sir Robert McAlpine (United Kingdom)
2000
Induction of transplantation tolerance with certain therapeutic nondepleting monoclonal antibodies can lead to a robust state peripheral “dominant” tolerance. Regulatory CD4+ T cells, which mediate this form tolerance, be isolated from spleens tolerant animals. To determine whether there were any extra-lymphoid sites that might harbor regulatory cells we sought their presence in tolerated skin allografts and normal skin. When grafts are retransplanted onto cell–depleted hosts,...
Follicular helper T (T(FH)) cells participate in humoral responses providing selection signals to germinal center B cells. Recently, expression of CXCR5, PD-1, and the transcription factor Bcl-6 has allowed identification T(FH) We found that a proportion follicular cells, with phenotypic characteristics expressing Foxp3, are recruited during course (GC) reaction. These Foxp3(+) derive from natural regulatory To establish vivo physiologic importance we used CXCR5-deficient which do not have...
Abstract Transplantation tolerance can be induced in mice by grafting under the cover of nondepleting CD4 plus CD8 or CD154 mAbs. This is donor Ag specific and depends on a population CD4+ regulatory T cells that, as yet, remain poorly defined terms their specificity, origin, phenotype. Blocking Ag-specific response vitro with an anti-CD4 mAb allowed from monospecific female TCR-transgenic against male Dby, presented H-2Ek, to express high levels foxP3 mRNA. induction was dependent TGF-β....
Abstract CD4+CD25+ T cells have been proposed as the principal regulators of both self-tolerance and transplantation tolerance. Although do a suppressive role in tolerance, so CD4+CD25− cells, although 10-fold less potent. Abs to CTLA-4, CD25, IL-10, IL-4 were unable abrogate suppression mediated by tolerant spleen excluding any these molecules critical agents suppression. from naive mice can also prevent rejection despite lack previous experience donor alloantigens. However, this requires...
Abstract Nondepleting anti-CD154 (CD40 ligand) mAbs have proven effective in inducing transplantation tolerance rodents and primates. In the induction phase, Ab therapy is known to enhance apoptosis of Ag reactive T cells. However, this may not be sole explanation for tolerance, as we show study that maintained through a dominant regulatory mechanism which, like induced with CD4 Abs, manifests infectious tolerance. Therefore, Abs involves only deletion potentially aggressive cells, but also...
Abstract Invariant NKT (iNKT) cells were shown to prevent the onset of experimental autoimmune encephalomyelitis in mice following administration their specific TCR agonist α-galactosylceramide. We found that this protection was associated with emergence a Foxp3+ iNKT cell population cervical lymph nodes. demonstrate differentiation these is critically dependent on TGF-β both and humans. Moreover, vivo generation observed TGF-β–rich environment murine gut. displayed phenotype similar...
Abstract Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines differential functions Tfh Tfr cells is unclear. Here we show antigen-specific after immunization are preferentially recruited GC become cells, but not also proliferate efficiently on restimulation with same immunizing antigen in vitro . Ex vivo TCR repertoire analysis shows induces oligoclonal...
Germinal center (GC) responses are controlled by T follicular helper (Tfh) and regulatory (Tfr) cells crucial for the generation of high-affinity antibodies. Although biology human circulating tissue Tfh has been established, relationship between blood Tfr defined as CXCR5+Foxp3+ remains elusive. We found that increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially patients high autoantibody titers, well healthy individuals upon influenza vaccination....
Objective To investigate whether the balance of blood follicular helper T (Tfh) cells and regulatory (Tfr) can provide information about ectopic lymphoid neogenesis disease activity in primary Sjögren's syndrome ( SS ). Methods We prospectively recruited 56 patients clinically suspected having . Sixteen these subsequently fulfilled American–European Consensus Group criteria for were compared to 16 with non‐ sicca syndrome. Paired minor salivary gland MSG ) biopsy samples analyzed study Tfr...
MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived (BM-MSCs), gold-standard in immunotherapy. Immunogenicity immunosuppression assessed by mixed lymphocyte reactions, suppression of proliferation induction regulatory T cells. Results showed that UCX less immunogenic higher activity than BM-MSCs. Further, did not need prior activation or priming exert effects. This was further corroborated vivo a...
Background Inhibiting programmed cell death protein 1 (PD-1) or PD-ligand (PD-L1) has shown exciting clinical outcomes in diverse human cancers. So far, only monoclonal antibodies are approved as PD-1/PD-L1 inhibitors. While significant observed on patients who respond to these therapeutics, a large proportion of the do not benefit from currently available immune checkpoint inhibitors, which strongly emphasize importance developing new immunotherapeutic agents. Methods In this study, we...
Abstract Breast cancer is the primary cause of cancer‐related death in women worldwide. subtypes are characterized by different gene expression patterns, which drive their prognostic factors and therapeutic options. Among them, triple‐negative breast (TNBC) one deadliest due to its aggressiveness, high rate early recurrence distant metastases, limited Despite recent approval monoclonal antibodies targeting programmed cell protein 1 (PD‐1) or ligand (PD‐L1) for treatment TNBC patients with a...
Abstract There is now compelling evidence for subpopulations of CD4+ T cells whose role to prevent immune pathology in both autoimmunity and transplantation. We have cloned against a male transplantation Ag that, unlike Th1 or Th2 clones, suppresses the rejection skin grafts are therefore considered examples regulatory cells. identified, using serial analysis gene expression, transcripts that overexpressed compared with clones. Some these increased tolerated rather than rejecting addition...
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset perpetuation of this disease. The main goal work was to determine whether cytokines driving neutrophil activation are dysregulated very early rheumatoid patients with less than 6 weeks duration before treatment (VERA). Cytokines related were quantified serum VERA established RA compared...