Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis
Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results fro...
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| Format: | Article |
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Wiley
2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/3642832 |
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| author | Charlene Hawkins Guzel Shaginurova D. Auriel Shelton Jose D. Herazo-Maya Kyra A. Oswald-Richter Joseph E. Rotsinger Anjuli Young Lindsay J. Celada Naftali Kaminski Carla Sevin Wonder P. Drake |
| author_facet | Charlene Hawkins Guzel Shaginurova D. Auriel Shelton Jose D. Herazo-Maya Kyra A. Oswald-Richter Joseph E. Rotsinger Anjuli Young Lindsay J. Celada Naftali Kaminski Carla Sevin Wonder P. Drake |
| author_sort | Charlene Hawkins |
| collection | DOAJ |
| description | Investigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis. We characterized sarcoidosis CD4+ T cell immune function in systemic and local environments among subjects undergoing disease progression compared to those experiencing disease resolution. Spontaneous and TCR-stimulated Th1 cytokine expression and proliferation assays were performed in 53 sarcoidosis subjects and 30 healthy controls. PD-1 expression and apoptosis were assessed by flow cytometry. Compared to healthy controls, sarcoidosis CD4+ T cells demonstrated reductions in Th1 cytokine expression, proliferative capacity (p<0.05), enhanced apoptosis (p<0.01), and increased PD-1 expression (p<0.001). BAL-derived CD4+ T cells also demonstrated multiple facets of T cell exhaustion (p<0.05). Reversal of CD4+ T cell exhaustion was observed in subjects undergoing spontaneous resolution (p<0.05). Sarcoidosis CD4+ T cells exhibit loss of cellular function during progressive disease that follows the archetype of T cell exhaustion. |
| format | Article |
| id | doaj-art-356f6b295db34b24a41ea1fa93709e95 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-356f6b295db34b24a41ea1fa93709e952025-02-03T01:24:13ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/36428323642832Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary SarcoidosisCharlene Hawkins0Guzel Shaginurova1D. Auriel Shelton2Jose D. Herazo-Maya3Kyra A. Oswald-Richter4Joseph E. Rotsinger5Anjuli Young6Lindsay J. Celada7Naftali Kaminski8Carla Sevin9Wonder P. Drake10Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USADivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USASection of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT 06520, USADivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USADivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USADivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USADivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USASection of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT 06520, USADivision of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USADivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USAInvestigation of the Th1 immune response in sarcoidosis CD4+ T cells has revealed reduced proliferative capacity and cytokine expression upon TCR stimulation. In other disease models, such cellular dysfunction has been associated with a step-wise, progressive loss of T cell function that results from chronic antigenic stimulation. T cell exhaustion is defined by decreased cytokine production upon TCR activation, decreased proliferation, increased expression of inhibitory cell surface receptors, and increased susceptibility to apoptosis. We characterized sarcoidosis CD4+ T cell immune function in systemic and local environments among subjects undergoing disease progression compared to those experiencing disease resolution. Spontaneous and TCR-stimulated Th1 cytokine expression and proliferation assays were performed in 53 sarcoidosis subjects and 30 healthy controls. PD-1 expression and apoptosis were assessed by flow cytometry. Compared to healthy controls, sarcoidosis CD4+ T cells demonstrated reductions in Th1 cytokine expression, proliferative capacity (p<0.05), enhanced apoptosis (p<0.01), and increased PD-1 expression (p<0.001). BAL-derived CD4+ T cells also demonstrated multiple facets of T cell exhaustion (p<0.05). Reversal of CD4+ T cell exhaustion was observed in subjects undergoing spontaneous resolution (p<0.05). Sarcoidosis CD4+ T cells exhibit loss of cellular function during progressive disease that follows the archetype of T cell exhaustion.http://dx.doi.org/10.1155/2017/3642832 |
| spellingShingle | Charlene Hawkins Guzel Shaginurova D. Auriel Shelton Jose D. Herazo-Maya Kyra A. Oswald-Richter Joseph E. Rotsinger Anjuli Young Lindsay J. Celada Naftali Kaminski Carla Sevin Wonder P. Drake Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis Journal of Immunology Research |
| title | Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis |
| title_full | Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis |
| title_fullStr | Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis |
| title_full_unstemmed | Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis |
| title_short | Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis |
| title_sort | local and systemic cd4 t cell exhaustion reverses with clinical resolution of pulmonary sarcoidosis |
| url | http://dx.doi.org/10.1155/2017/3642832 |
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