Rapid Functional Decline of Activated and Memory Graft-versus-Host-Reactive T Cells Encountering Host Antigens in the Absence of Inflammation
| Autor: | Guiling Zhao, Alicia L. Carlson, Giovanna Andreola, Megan Sykes, Charles P. Lin, Hao Wei Li, Steven Shao |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
CD4-Positive T-Lymphocytes
T cell Immunology Programmed Cell Death 1 Receptor Priming (immunology) chemical and pharmacologic phenomena Apoptosis Biology CD8-Positive T-Lymphocytes Lymphocyte Activation Article Interleukin 21 Graft vs Host Reaction Interferon-gamma Mice medicine Immunology and Allergy Cytotoxic T cell Animals IL-2 receptor Antigen-presenting cell Interleukin 3 Cell Proliferation Inflammation Mice Knockout Natural killer T cell Mice Inbred C57BL medicine.anatomical_structure Radiation Chimera Female Immunologic Memory |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 195(3) |
| ISSN: | 1550-6606 |
| Popis: | Inflammation in the priming host environment has critical effects on the graft-versus-host (GVH) responses mediated by naive donor T cells. However, it is unclear how a quiescent or inflammatory environment impacts the activity of GVH-reactive primed T and memory cells. We show in this article that GVH-reactive primed donor T cells generated in irradiated recipients had diminished ability compared with naive T cells to increase donor chimerism when transferred to quiescent mixed allogeneic chimeras. GVH-reactive primed T cells showed marked loss of cytotoxic function and activation, and delayed but not decreased proliferation or accumulation in lymphoid tissues when transferred to quiescent mixed chimeras compared with freshly irradiated secondary recipients. Primed CD4 and CD8 T cells provided mutual help to sustain these functions in both subsets. CD8 help for CD4 cells was largely IFN-γ dependent. TLR stimulation after transfer of GVH-reactive primed T cells to mixed chimeras restored their cytotoxic effector function and permitted the generation of more effective T cell memory in association with reduced PD-1 expression on CD4 memory cells. Our data indicate that an inflammatory host environment is required for the maintenance of GVH-reactive primed T cell functions and the generation of memory T cells that can rapidly acquire effector functions. These findings have important implications for graft-versus-host disease and T cell–mediated immunotherapies. |
| Databáze: | OpenAIRE |
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