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7 results on '"Duley, Amanda K."'

3. CXCR4 acts as a costimulator during thymic β-selection

Author

Trampont, Paul C, primary, Tosello-Trampont, Annie-Carole, additional, Shen, Yuelei, additional, Duley, Amanda K, additional, Sutherland, Ann E, additional, Bender, Timothy P, additional, Littman, Dan R, additional, and Ravichandran, Kodi S, additional

Published
2009
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5. CXCR4 acts as a costimulator during thymic β-selection.

Author

Trampont, Paul C., Tosello-Trampont, Annie-Carole, Shen, Yuelei, Duley, Amanda K., Sutherland, Ann E., Bender, Timothy P., Littman, Dan R., and Ravichandran, Kodi S.

Subjects
T cell receptors, LYMPHOCYTES, CHEMOKINES, ANTIGEN presenting cells, INFLAMMATORY mediators
Abstract

Passage through the β-selection developmental checkpoint requires productive rearrangement of segments of the T cell antigen receptor-β gene (Tcrb) and formation of a pre-TCR on the surface of CD4−CD8− thymocytes. How other receptors influence ββ-selection is less well understood. Here we define a new role for the chemokine receptor CXCR4 during T cell development. CXCR4 functionally associated with the pre-TCR and influenced β-selection by regulating the steady-state localization of immature thymocytes in thymic subregions, by facilitating optimal pre-TCR-induced survival signals, and by promoting thymocyte proliferation. We also characterize functionally relevant signaling molecules downstream of CXCR4 and the pre-TCR in thymocytes. Our data designate CXCR4 as a costimulator of the pre-TCR during β-selection. [ABSTRACT FROM AUTHOR]

Published
2010
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6. BLT-humanized C57BL/6 Rag2−/−γc−/−CD47−/−mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection

Author

Lavender, Kerry J., Pang, Wendy W., Messer, Ronald J., Duley, Amanda K., Race, Brent, Phillips, Katie, Scott, Dana, Peterson, Karin E., Chan, Charles K., Dittmer, Ulf, Dudek, Timothy, Allen, Todd M., Weissman, Irving L., and Hasenkrug, Kim J.

Abstract

The use of C57BL/6 Rag2−/−γc−/−mice as recipients for xenotransplantation with human immune systems (humanization) has been problematic because C57BL/6 SIRPα does not recognize human CD47, and such recognition is required to suppress macrophage-mediated phagocytosis of transplanted human hematopoietic stem cells (HSCs). We show that genetic inactivation of CD47on the C57BL/6 Rag2−/−γc−/−background negates the requirement for CD47-signal recognition protein α (SIRPα) signaling and induces tolerance to transplanted human HSCs. These triple-knockout, bone marrow, liver, thymus (TKO-BLT) humanized mice develop organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissue that demonstrate high levels of multilineage hematopoiesis. Importantly, these mice have an intact complement system and showed no signs of graft-versus-host disease (GVHD) out to 29 weeks after transplantation. Sustained, high-level HIV-1 infection was observed via either intrarectal or intraperitoneal inoculation. TKO-BLT mice exhibited hallmarks of human HIV infection including CD4+T-cell depletion, immune activation, and development of HIV-specific B- and T-cell responses. The lack of GVHD makes the TKO-BLT mouse a significantly improved model for long-term studies of pathogenesis, immune responses, therapeutics, and vaccines to human pathogens.

Published
2013
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7. CXCR4 acts as a costimulator during thymic beta-selection.

Author

Trampont PC, Tosello-Trampont AC, Shen Y, Duley AK, Sutherland AE, Bender TP, Littman DR, and Ravichandran KS

Subjects
Animals, B-Lymphocytes immunology, Blotting, Western, Cell Proliferation, Chemokine CXCL12 biosynthesis, Chemokine CXCL12 immunology, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluorescent Antibody Technique, Genes, T-Cell Receptor beta immunology, Immunoprecipitation, Lymphoid Progenitor Cells immunology, Mice, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes cytology, T-Lymphocytes immunology, Thymus Gland immunology, B-Lymphocytes cytology, Cell Differentiation immunology, Lymphoid Progenitor Cells cytology, Receptors, CXCR4 immunology, Thymus Gland cytology
Abstract

Passage through the beta-selection developmental checkpoint requires productive rearrangement of segments of the T cell antigen receptor-beta gene (Tcrb) and formation of a pre-TCR on the surface of CD4(-)CD8(-) thymocytes. How other receptors influence betabeta-selection is less well understood. Here we define a new role for the chemokine receptor CXCR4 during T cell development. CXCR4 functionally associated with the pre-TCR and influenced beta-selection by regulating the steady-state localization of immature thymocytes in thymic subregions, by facilitating optimal pre-TCR-induced survival signals, and by promoting thymocyte proliferation. We also characterize functionally relevant signaling molecules downstream of CXCR4 and the pre-TCR in thymocytes. Our data designate CXCR4 as a costimulator of the pre-TCR during beta-selection.

Published
2010
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