NK Cell Regulation of CD4 T Cell-Mediated Graft-versus-Host Disease
| Autor: | Kathleen Weatherly, Isabelle Salmon, Michel Y Braun, Marc Hazzan, Florence Gaudray, Magali Noval Rivas |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male T cell Immunology Graft vs Host Disease chemical and pharmacologic phenomena Cell Separation Biology Lymphocyte Activation Mice Interleukin 21 Killer Cells Natural -- immunology NK-92 Immunologie medicine Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cell Proliferation Mice Knockout Reverse Transcriptase Polymerase Chain Reaction CD4-Positive T-Lymphocytes -- immunology NK Cell Lectin-Like Receptor Subfamily K -- immunology Flow Cytometry NKG2D Adoptive Transfer Lymphocyte Activation -- immunology Cell biology Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K Graft vs Host Disease -- immunology Interleukin 12 Female |
| Zdroj: | The Journal of immunology, 184 (12 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0902598 |
| Popis: | CD3-negative NK cells are granular lymphocytes capable of producing inflammatory cytokines and killing malignant, infected, or stressed cells. We have recently observed a new role for NK cells in the control of the proliferation of CD4 T cells under persistent antigenic stimulation. Monoclonal anti-male CD4 T cells transferred into Rag2-/- male recipients did not expand or were rapidly eliminated. Remarkably, T cells transferred into NK cell-deficient Rag2-/- Il-2Rgammac-/- male hosts expanded extensively and mediated tissue lesions usually observed in chronic graft-versus-host disease (GVHD). T cell failure to proliferate and to induce chronic GVHD was the result of NK cell activity, because depletion of the recipient's NK1.1+ cells by Ab treatment induced T cell expansion and chronic GVHD. T cells under chronic Ag stimulation upregulated ligands of the activating receptor NKG2D, and regulatory activity of NK cells was inhibited by the injection of Abs directed to NKG2D. On the contrary, blocking NKG2A inhibitory receptors did not increase NK cell regulatory activity. Finally, we show that NK regulation of T cell expansion did not involve perforin-mediated lytic activity of NK cells, but depended on T cell surface expression of a functional Fas molecule. These results highlight the potential role played by NK cells in controlling the Ag-specific CD4+ T cells responsible for chronic GVHD. Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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