Article
Epinephrine suppresses integrin activity of stimulated cytomegalovirus-specific T cells in healthy humans
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Published: | August 29, 2016 |
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Background: Reactivation of latent viruses such as cytomegalovirus (CMV) may contribute to the initiation and progression of various autoimmune diseases. Efficient T cell immunity against CMV requires integrin-mediated adhesion of CMV-specific cytotoxic effector T cells to the endothelium or to virus-infected cells, which is induced by inside-out signaling following chemokine receptor or T cell receptor (TCR) stimulation, respectively. Previous analyses in healthy subjects indicated that epinephrine counteracts chemokine-induced inside-out signaling and in this way triggers de-adhesion of cytotoxic effector T cells from the endothelium.
Methods: To elucidate whether epinephrine suppresses integrin activity in TCR-stimulated cytotoxic T cells as well, we established a flow cytometric method that measures the binding of soluble multimeric intercellular adhesion molecule (ICAM)-1 complexes to beta2 integrins. CMV-specific T cells of healthy CMV-positive women and men were identified and stimulated using CMV peptide-major histocompatibility complex class I (pMHC) multimers in the presence or absence of epinephrine.
Results: Within 2 minutes of TCR activation by CMV pMHC multimers ICAM-1 binding on CMV-specific cytotoxic T cells was significantly increased, indicating a rapid beta2 integrin activation. This process was counteracted by epinephrine in a dose-dependent manner. Interestingly, physiological levels of epinephrine were sufficient to suppress beta2 integrin activity. Unstimulated T cells showed no ICAM-1 binding.
Conclusion: Epinephrine suppresses integrin activity in CMV-stimulated cytotoxic T cells and presumably impairs target cell killing. This neuroendocrine influence on T cell immunity directed against CMV could explain CMV reactivation in stressful conditions and might play a role for CMV reactivation in autoimmune diseases.