Helios marks strongly autoreactive CD4+ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-?B.
AuthorsDaley SR, Hu DY, Goodnow CC,
JournalJ Exp Med
PubMed ID23337809
'Acquisition of self-tolerance in the thymus requires T cells to discriminate strong versus weak T cell receptor binding by self-peptide-MHC complexes. We find this discrimination is reported by expression of the transcription factor Helios, which is induced during negative selection but decreases during positive selection. Helios and the proapoptotic protein ... More
B cell survival, surface BCR and BAFFR expression, CD74 metabolism, and CD8- dendritic cells require the intramembrane endopeptidase SPPL2A.
AuthorsBergmann H, Yabas M, Short A, Miosge L, Barthel N, Teh CE, Roots CM, Bull KR, Jeelall Y, Horikawa K, Whittle B, Balakishnan B, Sjollema G, Bertram EM, Mackay F, Rimmer AJ, Cornall RJ, Field MA, Andrews TD, Goodnow CC, Enders A,
JournalJ Exp Med
PubMed ID23267016
Druggable proteins required for B lymphocyte survival and immune responses are an emerging source of new treatments for autoimmunity and lymphoid malignancy. In this study, we show that mice with an inactivating mutation in the intramembrane protease signal peptide peptidase-like 2A (SPPL2A) unexpectedly exhibit profound humoral immunodeficiency and lack mature ... More
'In parallel' interconnectivity of the dorsal longitudinal anastomotic vessels requires both VEGF signaling and circulatory flow.
AuthorsZygmunt T, Trzaska S, Edelstein L, Walls J, Rajamani S, Gale N, Daroles L, Ramírez C, Ulrich F, Torres-Vázquez J,
JournalJ Cell Sci
PubMed ID22899709
Blood vessels deliver oxygen, nutrients, hormones and immunity factors throughout the body. To perform these vital functions, vascular cords branch, lumenize and interconnect. Yet, little is known about the cellular, molecular and physiological mechanisms that control how circulatory networks form and interconnect. Specifically, how circulatory networks merge by interconnecting 'in ... More
Single-molecule protein arrays enabled by scanning probe block copolymer lithography.
AuthorsChai J, Wong LS, Giam L, Mirkin CA,
JournalProc Natl Acad Sci U S A
PubMed ID22106270
The ability to control the placement of individual protein molecules on surfaces could enable advances in a wide range of areas, from the development of nanoscale biomolecular devices to fundamental studies in cell biology. Such control, however, remains a challenge in nanobiotechnology due to the limitations of current lithographic techniques. ... More
Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo.
AuthorsMandraju R, Murray S, Forman J, Pasare C,
Journal
PubMed ID24688022
TLR activation on dendritic cells (DCs) induces DC maturation and secretion of proinflammatory cytokines, both of which are important for activation and differentiation of CD4 T cells. The importance of TLR activation on DCs for CD8 T cell responses is less clear. In this study, we tested the ability of ... More
PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection.
AuthorsMacFarlane AW, Jillab M, Plimack ER, Hudes GR, Uzzo RG, Litwin S, Dulaimi E, Al-Saleem T, Campbell KS,
Journal
PubMed ID24764579
Programmed death-1 (PD-1) receptor is an inhibitory receptor on hematopoietic cells that can negatively regulate immune responses, particularly responses to tumors, which often upregulate PD-1 ligands. PD-1/PD-1 ligand blocking antibodies can reverse the inhibition and show significant therapeutic promise in treating renal cell carcinoma (RCC), lung cancer, and melanoma. While ... More
IL-2 coordinates IL-2-producing and regulatory T cell interplay.
AuthorsAmado IF, Berges J, Luther RJ, Mailhé MP, Garcia S, Bandeira A, Weaver C, Liston A, Freitas AA,
Journal
PubMed ID24249704
Many species of bacteria use quorum sensing to sense the amount of secreted metabolites and to adapt their growth according to their population density. We asked whether similar mechanisms would operate in lymphocyte homeostasis. We investigated the regulation of the size of interleukin-2 (IL-2)-producing CD4(+) T cell (IL-2p) pool using ... More
Semiautomated multiplexed quantum dot-based in situ hybridization and spectral deconvolution.
AuthorsByers RJ, Di Vizio D, O'connell F, Tholouli E, Levenson RM, Gossage K, Gossard K, Twomey D, Yang Y, Benedettini E, Rose J, Ligon KL, Finn SP, Golub TR, Loda M,
JournalJ Mol Diagn
PubMed ID17251332
Gene expression profiling has identified several potentially useful gene signatures for predicting outcome or for selecting targeted therapy. However, these signatures have been developed in fresh or frozen tissue, and there is a need to apply them to routinely processed samples. Here, we demonstrate the feasibility of a potentially high-throughput ... More
Enhanced innate antiviral gene expression, IFN-a, and cytolytic responses are predictive of mucosal immune recovery during simian immunodeficiency virus infection.
AuthorsVerhoeven D, George MD, Hu W, Dang AT, Smit-McBride Z, Reay E, Macal M, Fenton A, Sankaran-Walters S, Dandekar S,
Journal
PubMed ID24610016
The mucosa that lines the respiratory and gastrointestinal (GI) tracts is an important portal of entry for pathogens and provides the first line of innate immune defense against infections. Although an abundance of memory CD4(+) T cells at mucosal sites render them highly susceptible to HIV infection, the gut and ... More