The differentiation and protective capacity of Plasmodium-specific T cells are regulated by both positive and negative signals during malaria, but the molecular and cellular details remain poorly defined. Here we show that malaria patients and Plasmodium-infected rodents exhibit atypical expression of the co-stimulatory receptor OX40 on CD4 T cells and that therapeutic enhancement of OX40 signaling enhances helper CD4 T cell activity, humoral immunity, and parasite clearance in rodents. However, these beneficial effects of OX40 signaling are abrogated following coordinate blockade of PD-1 co-inhibitory pathways, which are also upregulated during malaria and associated with elevated parasitemia.
View Article and Find Full Text PDFFollowing infection, naïve CD4 T cells can differentiate into various functionally distinct effector and memory subsets, including T follicular helper (TFH) cells that orchestrate germinal center (GC) reactions necessary for high-affinity, pathogen-specific antibody responses. The origins and function of this cell type have been extensively examined in response to subunit immunization with model antigens. More recently, we are beginning to also appreciate the extent to which microbial infections shape the generation, function and maintenance of TFH cells.
View Article and Find Full Text PDFSp1 and Sp3 belong to the specificity proteins (Sp)/Krüppel-like transcription factor family. They are closely related, ubiquitously expressed, and recognize G-rich DNA motifs. They are thought to regulate generic processes such as cell-cycle and growth control, metabolic pathways, and apoptosis.
View Article and Find Full Text PDFRad23a and Rad23b proteins are linked to nucleotide excision DNA repair (NER) via association with the DNA damage recognition protein xeroderma pigmentosum group C (XPC) are and known to be implicated in protein turnover by the 26S proteasome. Rad23b-null mice are NER proficient, likely due to the redundant function of the Rad23b paralogue, Rad23a. However, Rad23b-null midgestation embryos are anemic, and most embryos die before birth.
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