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iNKT cells: innate lymphocytes with a diverse response

Publication . Monteiro, Marta; Graca, Luis

It is now established that natural killer T (NKT) cells can influence adaptive immune responses by producing vast amounts of cytokines. Different subsets of NKT cells with distinctive functional characteristics regarding cytokine production have been described. This is the case for NKT1, NKT2, or NKT17 that resemble conventional CD4 Th1, Th2, and Th17 cells in the cytokines they produce. Unlike conventional CD4 T cells that mostly acquire functional specialization in the periphery, a number of NKT cells become specialized effectors during thymic development. This opinion article describes the evidence for an extrathymic commitment of specialized NKT-cell subsets that, together with thymic lineages, contributes to the overall functional diversity of NKT cells participating in immune responses in the periphery.

2014Journal article

Restricted access

T follicular helper and T follicular regulatory cells have different TCR specificity

Publication . Maceiras, Ana Raquel; Almeida, Silvia Cristina Paiva; Mariotti-Ferrandiz, Encarnita; Chaara, Wahiba; Jebbawi, Fadi; Six, Adrien; Hori, Shohei; Klatzmann, David; Faro, Jose; Graca, Luis

Immunization leads to the formation of germinal centres (GCs) that contain both T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Whether T-cell receptor (TCR) specificity defines the differential functions of Tfh and Tfr cells is unclear. Here we show that antigen-specific T cells after immunization are preferentially recruited to the GC to become Tfh cells, but not Tfr cells. Tfh cells, but not Tfr cells, also proliferate efficiently on restimulation with the same immunizing antigen in vitro. Ex vivo TCR repertoire analysis shows that immunization induces oligoclonal expansion of Tfh cells. By contrast, the Tfr pool has a TCR repertoire that more closely resembles that of regulatory T (Treg) cells. Our data thus indicate that the GC Tfh and Tfr pools are generated from distinct TCR repertoires, with Tfh cells expressing antigen-responsive TCRs to promote antibody responses, and Tfr cells expressing potentially autoreactive TCRs to suppress autoimmunity.

2017Journal article

Open access