TCR-independent cytokine stimulation induces non-MHC-restricted T cell activity and is negatively regulated by HLA class I
| Autor: | Barbara Simm, Elisabeth H. Weiß, Dolores J. Schendel, Christine S. Falk, Monika Braun, Marion von Geldern |
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| Rok vydání: | 2006 |
| Předmět: |
Cytotoxicity
Immunologic T cell T-Lymphocytes Immunology CD1 Receptors Antigen T-Cell chemical and pharmacologic phenomena Biology Lymphocyte Activation Major Histocompatibility Complex Interleukin 21 medicine Immunology and Allergy Cytotoxic T cell Humans IL-2 receptor Receptors Immunologic cytokines cytotoxic T cells MHC natural killer cells Antigen-presenting cell Histocompatibility Antigens Class I Receptors Interleukin-2 NKG2D Cell biology medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K Cytokines Receptors Natural Killer Cell CD8 |
| Zdroj: | Eur. J. Immunol. 36, 2347-2358 (2006) |
| ISSN: | 0014-2980 |
| Popis: | Recent evidence suggests that the functional status of T cells activated independently from their TCR differs substantially from classical MHC-restricted T cells. Here, we show that TCR-independent, short-term stimulation via the common gamma-chain of the IL-2/IL-15 receptor induces non-MHC-restricted cytotoxicity and sustained cytokine secretion in purified CD4+ or CD8+ T cells. NK-like cytotoxicity is directed against MHC class I-negative targets and can be inhibited by classical and non-classical HLA class I molecules. Known inhibitory receptors, such as CD85j (ILT2) and leukocyte-associated Ig-like receptor-1, are not responsible for this HLA-mediated inhibition. NK-like cytotoxicity can be costimulated by NKG2D (CD314) triggering, but 2B4 (CD244) and DNAM-1 (CD226) are not involved. NK-like T cells display an activated phenotype and secrete various cytokines, including IFN-gamma, TNF-alpha, IL-5, IL-13 and MIP-1beta. Under normal conditions, HLA class I-mediated inhibition may function as a safety mechanism to prevent unbalanced cytokine production and effector killing mechanisms by T cells that were activated independently from their TCR. Non-MHC-restricted activity represents a functional status rather than a property of distinct T cell subpopulations. Thus, cytokine-induced, non-MHC-restricted T cells may be relevant in immune responses against tumors showing aberrant MHC expression through their capacities of cytokine production and direct tumor cell eradication. |
| Databáze: | OpenAIRE |
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