Innate signals overcome acquired TCR signaling pathway regulation and govern the fate of human CD161hi CD8α+ semi-invariant T cells
| Autor: | Shelly Heimfeld, Cameron J. Turtle, Ryan Basom, Laura Tabellini, Rochelle C. Joslyn, Colleen Delaney, Stanley R. Riddell, Jeff Delrow, Hillary M. Swanson, John A. Hansen |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_treatment
Cellular differentiation CD8 Antigens Receptors Antigen T-Cell alpha-beta Immunology Blotting Western Biology Lymphocyte Activation Biochemistry Proinflammatory cytokine Immunophenotyping T-Lymphocyte Subsets medicine Humans RNA Messenger Cells Cultured Immunobiology Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling T-cell receptor Hematopoietic stem cell CD28 Cell Differentiation Cell Biology Hematology Fetal Blood Flow Cytometry Cell biology medicine.anatomical_structure Cytokine Cytokines Signal transduction Biomarkers NK Cell Lectin-Like Receptor Subfamily B Signal Transduction |
| Popis: | Type 17 programmed CD161hiCD8α+ T cells contribute to mucosal immunity to bacteria and yeast. In early life, microbial colonization induces proliferation of CD161hi cells that is dependent on their expression of a semi-invariant Vα7.2+ TCR. Although prevalent in adults, CD161hiCD8α+ cells exhibit weak proliferative and cytokine responses to TCR ligation. The mechanisms responsible for the dichotomous response of neonatal and adult CD161hi cells, and the signals that enable their effector function, have not been established. We describe acquired regulation of TCR signaling in adult memory CD161hiCD8α+ T cells that is absent in cord CD161hi cells and adult CD161lo cells. Regulated TCR signaling in CD161hi cells was due to profound alterations in TCR signaling pathway gene expression and could be overcome by costimulation through CD28 or innate cytokine receptors, which dictated the fate of their progeny. Costimulation with IL-1β during TCR ligation markedly increased proinflammatory IL-17 production, while IL-12–induced Tc1-like function and restored the response to TCR ligation without costimulation. CD161hi cells from umbilical cord blood and granulocyte colony stimulating factor-mobilized leukaphereses differed in frequency and function, suggesting future evaluation of the contribution of CD161hi cells in hematopoietic stem cell grafts to transplant outcomes is warranted. |
| Databáze: | OpenAIRE |
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