- Biochemistry and Pharmacology - Research Publications
Biochemistry and Pharmacology - Research Publications
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ItemChewing the fat on natural killer T cell developmentGodfrey, DI ; McConville, MJ ; Pellicci, DG (ROCKEFELLER UNIV PRESS, 2006-10-02)Natural killer T cells (NKT cells) are selected in the thymus by self-glycolipid antigens presented by CD1d molecules. It is currently thought that one specific component of the lysosomal processing pathway, which leads to the production of isoglobotrihexosylceramide (iGb3), is essential for normal NKT cell development. New evidence now shows that NKT cell development can be disrupted by a diverse range of mutations that interfere with different elements of the lysosomal processing and degradation of glycolipids. This suggests that lysosomal storage diseases (LSDs) in general, rather than one specific defect, can disrupt CD1d antigen presentation, leading to impaired development of NKT cells.
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ItemExpression of the Glucocorticoid Receptor from the 1A Promoter correlates with T Lymphocyte Sensitivity to Glucocrticoid-Induced Cell DeathPURTON, JARED FRANKLIN ; MONK, JULIE ALEXANDRA ; LIDDICOAT, DOUGLAS ; KYPARISSOUDIS, KONSTANTINOS ; SAKKAL, SAMY ; RICHARDSON, SAMANTHA JANE ; GODFREY, DALE IAN ; COLE, TIMOTHY JAMES ( 2004)
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ItemWithout peripheral interference, thymic deletion is mediated in a cohort of double-positive cells without classical activationZhan, YF ; Purton, JF ; Godfrey, DI ; Cole, TJ ; Heath, WR ; Lew, AM (NATL ACAD SCIENCES, 2003-02-04)Peripheral activation can cause bystander thymocyte death by eliciting a "cytokine storm." This event complicates in vivo studies using exogenous ligand-induced models of negative selection. A stable transgenic model that selectively eliminates peripheral CD4 cells has allowed us to analyze negative selection as direct cognate events in two T cell receptor transgenic mice, OT-II and DO11. Whereas cognate peptide induced a massive deletion in double-positive (DP) cells in mice with peripheral CD4 cells, this DP deletion was modest in mice lacking peripheral CD4 cells. Using BrdUrd and annexin V staining, we found that negative selection primarily occurs in a cohort of DP cells and the absence of single-positive (SP) cells is largely caused by reduction in the cohort of DP precursors. Moreover, the fates of DP cells and SP cells after antigen exposure were vastly different. Whereas SP cells up-regulated uniformly their CD69 and CD44 levels, increased their cell size, and survived after antigen exposure, DP cells had less CD69 and CD44 up-regulation, no size change, and promptly died. Thus, negative selection represents an "abortive" activation different from activation-induced cell death of mature T cells.