TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu.
T cell apoptosis is critical to development and homeostasis of the immune system. The most salient feature of apoptosis is the lack of an attendant inflammatory response or tissue damage. Here, we present evidence that apoptotic T cells release TGF-beta, thereby contributing to an immunosuppressive milieu. Apoptotic T cells released not only latent but also bio-active TGF-beta. Nonetheless, TGF-beta transcription was not upregulated, suggesting release of existing rather than synthesis of new TGF-beta. Localized within the intracellular membrane-bound compartment, which includes mitochondria, TGF-beta was redistributed into the cytosol following loss of mitochondrial membrane potential. TGF-beta secreted from apoptotic T cells inhibited proinflammatory cytokine production by activated macrophages to foster immune suppression. These findings broaden the potential mechanisms whereby induction of immune tolerance or deficiency occurs through T cell deletion.
Chen
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W
Cellular Immunology Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. wchen@dir.nidcr.nih.gov
Frank
M E
ME
Jin
W
W
Wahl
S M
SM
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005720:Gamma Rays; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone