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Scooped by
Gilbert C FAURE
December 25, 2017 2:35 AM
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Scooped by
Gilbert C FAURE
December 24, 2017 6:57 AM
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The spatial reorganization of T cell receptors is critical for ligand discrimination
in T cell signaling.
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Scooped by
Gilbert C FAURE
December 21, 2017 10:52 AM
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Suggested by
Société Francaise d'Immunologie
December 21, 2017 3:24 AM
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Human CD3+CD4+ Th cells, FOXP3+ T regulatory (Treg) cells, and T regulatory type 1 (Tr1) cells are essential for ensuring peripheral immune response and tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully characterized. Independent functional characterization of human Th1, Th2, Th17, T follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface molecules, transcription factors, and signaling profiles for each subset. However, the adequacy of these markers to recapitulate the whole CD3+CD4+ T cell compartment remains questionable. In this study, we examined CD3+CD4+ T cell populations by single-cell mass cytometry. We characterize the CD3+CD4+ Th, Treg, and Tr1 cell populations simultaneously across 23 memory T cell–associated surface and intracellular molecules. High-dimensional analysis identified several new subsets, in addition to the already defined CD3+CD4+ Th, Treg, and Tr1 cell populations, for a total of 11 Th cell, 4 Treg, and 1 Tr1 cell subsets. Some of these subsets share markers previously thought to be selective for Treg, Th1, Th2, Th17, and Tfh cells, including CD194 (CCR4)+FOXP3+ Treg and CD183 (CXCR3)+T-bet+ Th17 cell subsets. Unsupervised clustering displayed a phenotypic organization of CD3+CD4+ T cells that confirmed their diversity but showed interrelation between the different subsets, including similarity between Th1–Th2–Tfh cell populations and Th17 cells, as well as similarity of Th2 cells with Treg cells. In conclusion, the use of single-cell mass cytometry provides a systems-level characterization of CD3+CD4+ T cells in healthy human blood, which represents an important baseline reference to investigate abnormalities of different subsets in immune-mediated pathologies.
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Scooped by
Gilbert C FAURE
December 20, 2017 1:00 PM
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The latest generation of cancer treatments spring from the discovery that the human immune system is able to beat the disease. Like Dorothy in "The Wizard of Oz," what research teams around the world have spent decades searchin
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Scooped by
Gilbert C FAURE
December 19, 2017 7:41 AM
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Scooped by
Gilbert C FAURE
December 18, 2017 11:13 AM
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bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
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Suggested by
Société Francaise d'Immunologie
December 18, 2017 6:53 AM
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Nat Commun. 2017 Dec 12;8(1):2078. doi: 10.1038/s41467-017-01526-z.
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Scooped by
Gilbert C FAURE
December 17, 2017 11:51 AM
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Two immunoglobulin (Ig) diversification mechanisms collaborate to provide protective humoral immunity. Combinatorial assembly of IgH and IgL V region exons from gene segments generates preimmune Ig repertoires, expressed as B cell receptors (BCRs). Secondary diversification occurs when Ig V regions undergo somatic hypermutation (SHM) and affinity-based selection toward antigen in activated germinal center (GC) B cells. Secondary diversification is thought to only ripen the antigen-binding affinity of Igs that already exist (i.e., cognate Igs) because of chance generation during preimmune Ig diversification. However, whether stochastic activation of noncognate B cells can generate new affinity to antigen in GCs is unclear. Using a mouse model whose knock-in BCR does not functionally engage with immunizing antigen, we found that chronic immunization induced antigen-specific serological responses with diverse SHM-mediated antibody affinity maturation pathways and divergent epitope targeting. Thus, intrinsic GC B cell flexibility allows for somatic, noncognate B cell evolution, permitting de novo antigen recognition and subsequent antibody affinity maturation without initial preimmune BCR engagement.
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Scooped by
Gilbert C FAURE
December 15, 2017 2:33 AM
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Myeloid-derived suppressor cells (MDSC) are one of the major components of the tumor
microenvironment. The main feature of these cells is their potent immune suppressive
activity. MDSC are generated in the bone marrow and, in tumor-bearing hosts, migrate
to peripheral lymphoid organs and the tumor to contribute to the formation of the
tumor microenvironment. Recent findings have revealed differences in the function
and fate of MDSC in the tumor and peripheral lymphoid organs. We review these findings
here and, in this context, we discuss the current understanding as to the nature of
these differences, the underlying mechanisms, and their potential impact on the regulation
of tumor progression.
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Scooped by
Gilbert C FAURE
December 15, 2017 2:31 AM
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The online version of Trends in Immunology at ScienceDirect.com, the world's leading platform for high quality peer-reviewed full-text journals.
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Scooped by
Gilbert C FAURE
December 12, 2017 2:24 AM
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Scooped by
Gilbert C FAURE
December 10, 2017 6:13 AM
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Scooped by
Gilbert C FAURE
December 24, 2017 3:36 PM
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Beyond their role in neutralization, antibodies mediate functions such as phagocytosis,
cytotoxicity, and maintenance of immune homeostasis. Two modifications to the constant
domain control antibody activity: theirreversible genomic selection of isotype/subclass
and alterations in glycosylation. Because glycosylation alters the affinity of antibodies
for Fc receptors, evidence suggests that glycosylation is a central mechanism for
the immune system to tune a broad range of biological activities.
Memory T cells protect against previously encountered pathogens, but their origins are unclear. Two studies track DNA modifications over time and find that these cells arise from effector T cells.
Via Krishan Maggon
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Suggested by
Société Francaise d'Immunologie
December 21, 2017 3:24 AM
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Although memory B cells sustain long-term humoral immunity, the nature of their precursors
within the germinal center has remained elusive. Suan et al. demonstrate that these
cells are uniquely identified by CCR6 expression in both mouse and human germinal
centers, that they are the most quiescent B cells in these structures, and that they
are generated within the light zone. Memory B cell precursors have a primarily low
affinity for antigen but also include cells emerging from the high-affinity compartment.
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Suggested by
LIGHTING
December 20, 2017 1:25 PM
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Type-2-cell-mediated immune responses play critical roles in regulating host resistance
against helminths and promoting tissue repair and metabolic homeostasis. Harris and
Loke review recent advances in the field resulting from studies of helminth-host interactions
and provide insight into the activation and function of type 2 immune cells.
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Suggested by
LIGHTING
December 19, 2017 11:30 AM
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Scooped by
Gilbert C FAURE
December 18, 2017 11:16 AM
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bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
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Scooped by
Gilbert C FAURE
December 18, 2017 11:13 AM
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Group 2 innate lymphoid cells (ILC2s) are effector cells within the mucosa and key participants in type 2 immune responses in the context of allergic inflammation and infection. ILC2s develop in the bone marrow from common lymphoid progenitor cells, but little is known about how ILC2s egress from the bone marrow for hematogenous trafficking. In this study, we identified a critical role for IL-33, a hallmark peripheral ILC2-activating cytokine, in promoting the egress of ILC2 lineage cells from the bone marrow. Mice lacking IL-33 signaling had normal development of ILC2s but retained significantly more ILC2 progenitors in the bone marrow via augmented expression of CXCR4. Intravenous injection of IL-33 or pulmonary fungal allergen challenge mobilized ILC2 progenitors to exit the bone marrow. Finally, IL-33 enhanced ILC2 trafficking to the lungs in a parabiosis mouse model of tissue disruption and repopulation. Collectively, these data demonstrate that IL-33 plays a critical role in promoting ILC2 egress from the bone marrow.
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Scooped by
Gilbert C FAURE
December 17, 2017 12:05 PM
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Scooped by
Gilbert C FAURE
December 16, 2017 2:46 AM
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NKT cells are required for the initial formation of germinal centers and production
of effective neutralizing antibody responses against viruses.
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Scooped by
Gilbert C FAURE
December 15, 2017 2:31 AM
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Innate lymphoid cells (ILCs) were identified principally as non‐T‐cell sources of key cytokines, able to provide rapid and early production of these molecules in the support of tissue homeostasis
Research Highlight
Platelets actively migrate at inflamed sites and can collect and bundle bacteria and promote neutrophil activation.
Via Krishan Maggon
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Suggested by
LIGHTING
December 11, 2017 12:11 PM
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Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation and guide their differentiation and immunoglobulin isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-γ. IL-21 and IFN-γ are coexpressed by Tfh cells during viral infections, but transcriptional regulation of these cytokines is not completely understood. In this study, we show that the T helper type 1 cell (Th1 cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh cells after acute viral infection, with a temporal decline in T-bet in the waning response. T-bet is important for Tfh cell production of IFN-γ, but not IL-21, and for a robust GC reaction. STAT4, phosphorylated in Tfh cells upon infection, is required for expression of T-bet and Bcl6 and for IFN-γ and IL-21. These data indicate that T-bet is expressed with Bcl6 in Tfh cells and is required alongside STAT4 to coordinate Tfh cell IL-21 and IFN-γ production and for promotion of the GC response after acute viral challenge.
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