The molecular signature of murine T cell homeostatic proliferation reveals both inflammatory and immune inhibition patterns
| Autor: | James W. Austin, Karen A. Fortner, Jeremy M. Boss, Ralph C. Budd, Jeffrey P. Bond |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine Cell Survival T cell Programmed Cell Death 1 Receptor Immunology Receptors Antigen T-Cell Mice Transgenic Biology Lymphocyte Activation Article Immunomodulation Mice 03 medical and health sciences Interleukin 21 0302 clinical medicine Downregulation and upregulation T-Lymphocyte Subsets medicine Animals Homeostasis Immunology and Allergy Cytotoxic T cell Antigen-presenting cell Cell Proliferation Inflammation Gene Expression Profiling CD44 Computational Biology Fas receptor Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure biology.protein Female Transcriptome Biomarkers CD8 030215 immunology |
| Zdroj: | Journal of Autoimmunity. 82:47-61 |
| ISSN: | 0896-8411 |
| Popis: | T lymphocyte homeostatic proliferation, driven by the engagement of T cell antigen receptor with self-peptide/major histocompatibility complexes, and signaling through the common γ-chain-containing cytokine receptors, is critical for the maintenance of the T cell compartment and is regulated by the Fas death receptor (Fas, CD95). In the absence of Fas, Fas-deficient lymphoproliferation spontaneous mutation (Ipr) mice accumulate homeostatically expanded T cells. The functional consequences of sequential rounds of homeostatic expansion are not well defined. We thus examined the gene expression profiles of murine wild-type and Fas-deficient Ipr CD8+ T cell subsets that have undergone different amounts of homeostatic proliferation as defined by their level of CD44 expression, and the CD4−CD8−TCRαβ+ T cell subset that results from extensive homeostatic expansion of CD8+ T cells. Our studies show that recurrent T cell homeostatic proliferation results in global gene expression changes, including the progressive upregulation of both cytolytic proteins such as Fas-Ligand and granzyme B as well as inhibitory proteins such as programmed cell death protein 1 (PD-1) and lymphocyte activating 3 (Lag3). These findings provide an explanation for how augmented T cell homeostatic expansion could lead to the frequently observed clinical paradox of simultaneous autoinflammatory and immunodeficiency syndromes and provide further insight into the regulatory programs that control chronically stimulated T cells. |
| Databáze: | OpenAIRE |
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