CD8 single-cell gene coexpression reveals three different effector types present at distinct phases of the immune response
Autor: | Marta Monteiro, Benedita Rocha, Henrique Veiga-Fernandes, Ivana Munitic, César Evaristo, Antonio Peixoto, Alain Charbit |
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Rok vydání: | 2007 |
Předmět: |
CD8 T cells
CD8 T cell differentiation primary responses secondary responses Immunology Antigen presentation CD8-Positive T-Lymphocytes Biology Article Mice Antigen T-Lymphocyte Subsets Animals Immunology and Allergy Cytotoxic T cell Antigens Antigen-presenting cell Immunity Cellular Lymphokine-activated killer cell Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling ZAP70 Cell Differentiation Articles Cytotoxicity Tests Immunologic Natural killer T cell Molecular biology Mice Inbred C57BL Gene Expression Regulation Microscopy Fluorescence Interleukin 12 Cytokines Female |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
DOI: | 10.1084/jem.20062349 |
Popis: | To study in vivo CD8 T cell differentiation, we quantified the coexpression of multiple genes in single cells throughout immune responses. After in vitro activation, CD8 T cells rapidly express effector molecules and cease their expression when the antigen is removed. Gene behavior after in vivo activation, in contrast, was quite heterogeneous. Different mRNAs were induced at very different time points of the response, were transcribed during different time periods, and could decline or persist independently of the antigen load. Consequently, distinct gene coexpression patterns/different cell types were generated at the various phases of the immune responses. During primary stimulation, inflammatory molecules were induced and down-regulated shortly after activation, generating early cells that only mediated inflammation. Cytotoxic T cells were generated at the peak of the primary response, when individual cells simultaneously expressed multiple killer molecules, whereas memory cells lost killer capacity because they no longer coexpressed killer genes. Surprisingly, during secondary responses gene transcription became permanent. Secondary cells recovered after antigen elimination were more efficient killers than cytotoxic T cells present at the peak of the primary response. Thus, primary responses produced two transient effector types. However, after boosting, CD8 T cells differentiate into long-lived killer cells that persist in vivo in the absence of antigen. |
Databáze: | OpenAIRE |
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