CD4-positive T cells articles from across Nature Portfolio

Dense-core granules (DCG) store insulin in pancreatic β cells. Here the authors show that crinosome, formed by fusing lysosome and DCGs, are pathogenic in mouse models of type 1 diabetes by diversifying local insulin epitopes beyond those tolerizing ones expressed in the thymus, thereby inducing autoreactive CD4 T cells for β cell death and insulin deficiency.

CD38 has been reported to be upregulated on T cells in lupus with unclear functional consequences. Here the authors show that CD4⁺CD38⁺ T cells from lupus patients have altered calcium homeostasis accompanied by alteration in cell membrane lipid composition and a suppression of IL-2.

Inflammatory intestinal lesions are often hypoxic, which results in the stabilization and activation of hypoxia-inducible-factors (HIF). Here authors show that in a mouse model of colitis, HIF-2α is specifically stabilized in CD4+ type 1T helper (T_H1) cells, leading to the upregulation of miR-29a expression and suppression of T_H1 cell function, which pathway is potentially targetable for therapeutic purposes.

Regulatory T cells (Tregs) are known for suppressing inflammatory processes, but their full capacity for tissue regeneration is yet to be harnessed. Here, the authors demonstrate the efficiency of Tregs in facilitating tissue healing in mouse models of bone, muscle, and skin injury, with monocytes/macrophages and interleukin-10 playing a key mechanistic role in the process.

Lymphocyte activation gene-3 (LAG3) is an immune checkpoint protein recently approved as a target for anti-melanoma therapy. Here, the authors solve the structure of mouse LAG3 bound to MHC-II to show that LAG3 blocks MHC-II/CD4 interactions, thereby implicating a potential mechanism of LAG3-mediated immune suppression.

Longitudinal sampling of human lymph nodes using fine-needle aspiration after influenza or SARS-CoV-2 vaccination reveals substantial durability and transcriptional reprogramming of follicular helper T cells over time.

Why some individuals ‘resist’ infection with Mycobacterium tuberculosis (Mtb) has been an enigma. Enriched T cell phenotypes have now been linked to ‘resistance’ to Mtb infection and disease across multiple cohorts.