Human Mucosal-Associated Invariant T Cells in Older Individuals Display Expanded TCRαβ Clonotypes with Potent Antimicrobial Responses
| Autor: | Katherine Kedzierska, Dale I. Godfrey, Liyen Loh, James McCluskey, Carolien E. van de Sandt, Nicholas A Gherardin, E. Kaitlynn Allen, Paul G. Thomas, Sidonia B G Eckle, Martha Lappas, Thomas Loudovaris, Ludivine Grzelak, Jane Crowe, Kylie M. Quinn, Jeremy Chase Crawford, Hui-Fern Koay, Sneha Sant, Katie L. Flanagan, Nicola L. Bird, Marcela de Lima Moreira, Jamie Rossjohn |
|---|---|
| Přispěvatelé: | Landsteiner Laboratory |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Chemokine Receptors Antigen T-Cell alpha-beta medicine.medical_treatment T cell Immunology Mucosal associated invariant T cell CD8-Positive T-Lymphocytes Biology CD8-Positive T-Lymphocytes/immunology Granzymes Mucosal-Associated Invariant T Cells GZMB Interferon-gamma 03 medical and health sciences alpha-beta/immunology 0302 clinical medicine Immune system Granzymes/immunology Antigen Lysosomal-Associated Membrane Protein 1 Receptors Escherichia coli medicine Humans Immunology and Allergy Lysosomal-Associated Membrane Protein 1/immunology Aged Escherichia coli/immunology Tumor Necrosis Factor-alpha Middle Aged T-Cell Tumor Necrosis Factor-alpha/immunology Viruses/immunology Cytokine medicine.anatomical_structure Receptors Antigen T-Cell alpha-beta/immunology Interferon-gamma/immunology Viruses biology.protein Female Mucosal-Associated Invariant T Cells/immunology CD8 030215 immunology |
| Zdroj: | Journal of immunology (Baltimore, Md., 204(5), 1119-1133. American Association of Immunologists The Journal of Immunology |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1900774 |
| Popis: | Mucosal-associated invariant T (MAIT) cells are important for immune responses against microbial infections. Although known to undergo marked numerical changes with age in humans, our understanding of how MAIT cells are altered during different phases across the human life span is largely unknown. Although also abundant in the tissues, our study focuses on MAIT cell analyses in blood. Across the human life span, we show that naive-like MAIT cells in umbilical cord blood switch to a central/effector memory-like profile that is sustained into older age. Whereas low-grade levels of plasma cytokine/chemokine were apparent in older donors (>65 y old), surprisingly, they did not correlate with the ex vivo MAIT hyperinflammatory cytokine profile observed in older adults. Removal of MAIT cells from older individuals and an aged environment resulted in the reversal of the baseline effector molecule profile comparable with MAIT cells from younger adults. An upregulated basal inflammatory profile accounted for reducedEscherichia coli–specific responses in aged MAIT cells compared with their young adult counterparts when fold change in expression levels of GzmB, CD107a, IFN-γ, and TNF was examined. However, the magnitude of antimicrobial MR1-dependent activation remained as potent and polyfunctional as with younger adults. Paired TCRαβ analyses of MAIT cells revealed large clonal expansions in older adults and tissues that rivalled, remarkably, the TCRαβ repertoire diversity of virus-specific CD8+T cells. These data suggest that MAIT cells in older individuals, although associated with large clonal TCRαβ expansions and increased baseline inflammatory potential, demonstrate plasticity and provide potent antimicrobial immunity. |
| Databáze: | OpenAIRE |
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