In Vivo Persistence of Codominant Human CD8+ T Cell Clonotypes Is Not Limited by Replicative Senescence or Functional Alteration
| Autor: | Marc Bruyninx, Estelle Devevre, Pedro Romero, Patricia Corthesy, Nathalie Rufer, Laurent Derré, Cédric Touvrey, Verena Voelter, Hanspeter Pircher, Daniel E. Speiser, Petra Baumgaertner, Yolanda D. Mahnke |
|---|---|
| Přispěvatelé: | Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Swiss Institute for Experimental Cancer Research - Lausanne (ISREC), Swiss Institute for Experimental Cancer Research, National Institutes of Health [Bethesda] (NIH), University of Freiburg [Freiburg] |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Senescence
Skin Neoplasms Time Factors Cellular differentiation T cell [SDV]Life Sciences [q-bio] Immunology Receptors Antigen T-Cell Epitopes T-Lymphocyte Biology CD8-Positive T-Lymphocytes Acetyltransferases/immunology Antigens Neoplasm/immunology CD8-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/pathology Cell Aging/immunology Cell Differentiation/immunology Cell Proliferation Epitopes T-Lymphocyte/immunology Follow-Up Studies HLA-A2 Antigen/immunology Humans Immunologic Memory Lymph Nodes/immunology Lymph Nodes/pathology Lymphatic Metastasis Melanoma/immunology Melanoma/pathology Middle Aged Neoplasm Proteins/immunology Peptides/immunology Receptors Antigen T-Cell/immunology Skin Neoplasms/immunology Skin Neoplasms/pathology Telomere/immunology Viruses/immunology Epitope 03 medical and health sciences 0302 clinical medicine Acetyltransferases Antigens Neoplasm HLA-A2 Antigen medicine Immunology and Allergy Cytotoxic T cell Melanoma Cellular Senescence 030304 developmental biology 0303 health sciences Cell growth Effector Cell Differentiation Telomere Neoplasm Proteins medicine.anatomical_structure Viruses Lymph Nodes Peptides [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology 030215 immunology |
| Zdroj: | Journal of Immunology, vol. 179, no. 4, pp. 2368-2379 Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2007, 179 (4), pp.2368-2379. ⟨10.4049/jimmunol.179.4.2368⟩ |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.179.4.2368⟩ |
| Popis: | T cell responses to viral epitopes are often composed of a small number of codominant clonotypes. In this study, we show that tumor Ag-specific T cells can behave similarly. In a melanoma patient with a long lasting HLA-A2/NY-ESO-1-specific T cell response, reaching 10% of circulating CD8 T cells, we identified nine codominant clonotypes characterized by individual TCRs. These clonotypes made up almost the entire pool of highly differentiated effector cells, but only a fraction of the small pool of less differentiated “memory” cells, suggesting that the latter serve to maintain effector cells. The different clonotypes displayed full effector function and expressed TCRs with similar functional avidity. Nevertheless, some clonotypes increased, whereas others declined in numbers over the observation period of 6 years. One clonotype disappeared from circulating blood, but without preceding critical telomere shortening. In turn, clonotypes with increasing frequency had accelerated telomere shortening, correlating with strong in vivo proliferation. Interestingly, the final prevalence of the different T cell clonotypes in circulation was anticipated in a metastatic lymph node withdrawn 2 years earlier, suggesting in vivo clonotype selection driven by metastases. Together, these data provide novel insight in long term in vivo persistence of T cell clonotypes associated with continued cell turnover but not replicative senescence or functional alteration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|