Dominant human CD8 T cell clonotypes persist simultaneously as memory and effector cells in memory phase
| Autor: | Estelle Devevre, Nathalie Rufer, Patricia Corthesy, Cédric Touvrey, Laurent Derré, Daniel E. Speiser, Pedro Romero |
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| Přispěvatelé: | Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV) |
| Rok vydání: | 2009 |
| Předmět: |
Cytotoxicity
Immunologic T cell [SDV]Life Sciences [q-bio] Immunology Streptamer CD8-Positive T-Lymphocytes Granzymes Immunophenotyping Interleukin-7 Receptor alpha Subunit 03 medical and health sciences Interleukin 21 0302 clinical medicine CD28 Antigens medicine Immunology and Allergy Cytotoxic T cell Humans IL-2 receptor Antigen-presenting cell 030304 developmental biology 0303 health sciences CD40 biology Perforin Cell Differentiation Natural killer T cell Cell biology Clone Cells medicine.anatomical_structure biology.protein Immunologic Memory [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2009, 182 (11), pp.6718-6726. ⟨10.4049/jimmunol.0803095⟩ |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0803095⟩ |
| Popis: | The adaptive immune system plays a critical role in protection at the time of secondary infection. It does so through the rapid and robust reactivation of memory T cells which are maintained long-term, in a phenotypically heterogeneous state, following their primary encounter with Ag. Although most HLA-A*0201/influenza matrix protein58–66-specific CD8 T cells from healthy donors display characteristics typical of memory T cells, through our extensive phenotypic analysis we have further shown that up to 20% of these cells express neither the IL-7 receptor CD127 nor the costimulatory molecule CD28. In contrast to the majority of CD28pos cells, granzyme B and perforin were frequently expressed by the CD28neg cells, suggesting that they are effector cells. Indeed, these cells were able to kill target cells, in an Ag-specific manner, directly ex vivo. Thus, our findings demonstrate the remarkable long-term persistence in healthy humans of not only influenza-specific memory cells, but also of effector T cells. We further observed that granzyme B expression in influenza-specific CD8 T cells paralleled levels in the total CD8 T cell population, suggestive of Ag-nonspecific bystander activation. Sequencing of TCR α- and β-chains showed that the TCR repertoire specific for this epitope was dominated by one, or a few, T cell clonotype per healthy donor. Moreover, our sequencing analysis revealed, for the first time in humans, that identical clonotypes can coexist as both memory and effector T cells, thereby supporting the principle of multipotent clonotypic differentiation. |
| Databáze: | OpenAIRE |
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