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PD-1 and ICOS are coexpressed in T follicular helper cells but define three sta...

Ribeiro, Filipa; Antunes, Diogo; Pires, Ana R.; Rino, José; Filipe, Beatriz; Jesus, Kátia; Correia, Ricardo; Fonseca, Válter R; Kumar, Saumya

Humoral responses to infection or vaccination require T cell-B cell interactions. T follicular helper (TFH) cells drive germinal center (GC) responses by providing help to B cells, whereas T follicular regulatory (TFR) cells regulate them. Both mature GC-located TFH and TFR cells are widely characterized by the expression of ICOS and PD-1. However, although human TFR cells share many phenotypic characteristics ...


T follicular regulatory cells keep B cell-directed autoreactivity in check

Ribeiro, Filipa; Graca, Luis

The immune system well illustrates the need for balance between aggression and tolerance: mechanisms are needed to drive the production of antibodies effective against pathogens whilst preventing the emergence of antibodies targeting our own cells. T follicular regulatory cells can suppress spontaneous antibody-mediated autoimmunity by vetoing B cell-directed reactivity.


Rapid progression of CD8 and CD4 T cells to cellular exhaustion and senescence ...

Pedroso, Rodrigo B.; Torres, Lícia; Ventura, Lucas Araújo; Camatta, Giovanna Caliman; Mota, Catarina; Mendes, Ana Catarina; Ribeiro, Filipa

Risk factors for the development of severe COVID-19 include several comorbidities, but age was the most striking one since elderly people were disproportionately affected by SARS-CoV-2 infection. Among the reasons for this markedly unfavorable response in the elderly, immunosenescence and inflammaging appear as major drivers of this outcome. A finding that was also notable was that hospitalized patients with se...


Stability of hybrid versus vaccine immunity against BA.5 infection over 8 months

Malato, João; Ribeiro, Ruy; Fernandes, Eugénia; Leite, Pedro Pinto; Casaca, Pedro; Antunes, Carlos; Fonseca, Valter R; Gomes, MC; Graca, Luis

The coverage of SARS-CoV-2 vaccination in large parts of the world, together with the high number of breakthrough infections, especially following the emergence of Omicron subvariants, makes hybrid immunity (resulting from vaccine and infection) common. Hybrid immunity, particularly after BA.1 or BA.2 infection, confers substantial protection against the BA.5 infection. However, although the waning of protectio...


Different antibody-associated autoimmune diseases have distinct patterns of T f...

Ribeiro, Filipa; Romão, Vasco C.; Rosa, Sara; Jesus, Kátia; Agua-Doce, Ana; Barreira, Sofia; Martins, Patrícia; Silva, Susana; Nobre, Ema

Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in pa...


S100B inhibition protects from chronic experimental autoimmune encephalomyelitis

Barros, Catarina; Barateiro, Andreia; Neto, Alexandre; Soromenho, Beatriz; Basto, Afonso; Mateus, Joana; Xapelli, Sara; Sebastião, Ana M; Brites, Dora

Studies have correlated excessive S100B, a small inflammatory molecule, with demyelination and associated inflammatory processes occurring in multiple sclerosis. The relevance of S100B in multiple sclerosis pathology brought an emerging curiosity highlighting its use as a potential therapeutic target to reduce damage during the multiple sclerosis course, namely during inflammatory relapses. We examined the rele...


Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors...

Acúrcio, Rita C; Pozzi, Sabina; Carreira, Barbara; Pojo, Marta; Gómez-Cebrián, Nuria; Casimiro, Sandra; Fernandes, Adelaide; Barateiro, Andreia

Background: Inhibiting programmed cell death protein 1 (PD-1) or PD-ligand 1 (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 clinical outcomes are observed on patients who respond to these therapeutics, a large proportion of the patients do not benefit from the currently available immune checkpoint...


Micro RNAs in Tfh regulation : small molecules with a big impact

Basto, Afonso; Graca, Luis

The germinal center (GC) reactions are critical for the production of high-affinity antibodies that comprise the protective humoral response elicited by infection or vaccination. GCs are initiated through the interaction of B cells with T follicular helper (Tfh) cells. While the transcriptional regulation of Tfh differentiation has been studied in great detail, the impact of micro RNAs (miRNAs) on Tfh developme...


Micro RNAs in Tfh regulation : small molecules with a big impact

Basto, Afonso P.; Graca, Luis

ABSTRACT - The germinal center (GC) reactions are critical for the production of high-affinity antibodies that comprise the protective humoral response elicited by infection or vaccination. GCs are initiated through the interaction of B cells with T follicular helper (Tfh) cells. While the transcriptional regulation of Tfh differentiation has been studied in great detail, the impact of micro RNAs (miRNAs) on Tf...


Peptidylprolyl isomerase C (Ppic) regulates invariant Natural Killer T cell (iN...

Paiva, Ricardo S.; Ramos, Camila V.; Azenha, Sara R.; Alves, Carolina; Basto, Afonso; Graca, Luis; Martins, Vera C.

Peptidyl-prolyl cis-trans isomerase C (Ppic) is expressed in several bone marrow (BM) hematopoietic progenitors and in T-cell precursors. Since the expression profile of Ppic in the hematoimmune system was suggestive that it could play a role in hematopoiesis and/or T lymphocyte differentiation, we sought to test that hypothesis in vivo. Specifically, we generated a Ppic-deficient mouse model by targeting the e...


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