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Through immune memory, infections have a lasting effect on the host. While memory cells enable accelerated and enhanced responses upon rechallenge with the same pathogen, their impact on susceptibility to unrelated diseases is unclear. We identify a subset of memory T helper 1 (Th1) cells termed innate acting memory T (TIA) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory TIA cells is induced in response to IL-12 in combination with IL-18 or IL-33 but is TCR independent. Rapid IFN-γ production by memory TIA cells is protective in subsequent heterologous challenge with the bacterial pathogen Legionella pneumophila. In contrast, antigen-independent reactivation of CD4+ memory TIA cells accelerates disease onset in an autoimmune model of multiple sclerosis. Our findings demonstrate that memory Th1 cells can acquire additional TCR-independent functionality to mount rapid, innate-like responses that modulate susceptibility to heterologous challenges. [ABSTRACT FROM AUTHOR]

Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact. A focused transcriptome analysis at single cell level allowed the dissection of the CD8 positive B cell population. We found that the affected cells are characteristically of the CD27+CD200- phenotype, and consist of two discrete late-stage subpopulations that carry signatures of activated memory B like cells, and early plasmablasts. Thus, there is only a restricted time window in the differentiation process during which B cells can intimately interact with CD8+ T cells. The findings point to a novel link between the T and B arms of the adaptive immune system, and suggest that CD8+ T cells have the capability to directly shape the global antibody repertoire. [ABSTRACT FROM AUTHOR]

GPBAR1(also known as TGR5) is a G-protein-coupled receptor (GPCR)that triggers intracellular signals upon ligation by various bileacids. The receptor has been studied mainly for its function in energyexpenditure and glucose homeostasis, and there is little informationon the role of GPBAR1 in the context of inflammation. After a high-throughputscreening campaign, we identified isonicotinamides exemplified bycompound 3as nonsteroidal GPBAR1 agonists. We optimizedthis series to potent derivatives that are active on both human andmurine GPBAR1. These agonists inhibited the secretion of the proinflammatorycytokines TNF-α and IL-12 but not the antiinflammatory IL-10in primary human monocytes. These effects translate in vivo, as compound 15inhibits LPS induced TNF-α andIL-12 release in mice. The response was GPBAR1 dependent, as demonstratedusing knockout mice. Furthermore, agonism of GPBAR1 stabilized thephenotype of the alternative, noninflammatory, M2-like type cellsduring differentiation of monocytes into macrophages. Overall, ourresults illustrate an important regulatory role for GPBAR1 agonistsas controllers of inflammation. [ABSTRACT FROM AUTHOR]