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Local and Systemic CD4+ T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis
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نویسنده
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hawkins c. ,shaginurova g. ,shelton d.a. ,herazo-maya j.d. ,oswald-richter k.a. ,rotsinger j.e. ,young a. ,celada l.j. ,kaminski n. ,sevin c. ,drake w.p.
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منبع
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journal of immunology research - 2017 - دوره : 2017 - شماره : 0
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چکیده
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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. © 2017 charlene hawkins et al.
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آدرس
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division of infectious diseases,department of medicine,vanderbilt university,school of medicine,nashville,tn, United States, department of pathology,microbiology and immunology,vanderbilt university,school of medicine,nashville,tn, United States, division of infectious diseases,department of medicine,vanderbilt university,school of medicine,nashville,tn, United States, section of pulmonary,critical care and sleep medicine,yale school of medicine,new haven,ct, United States, division of infectious diseases,department of medicine,vanderbilt university,school of medicine,nashville,tn, United States, division of infectious diseases,department of medicine,vanderbilt university,school of medicine,nashville,tn, United States, division of infectious diseases,department of medicine,vanderbilt university,school of medicine,nashville,tn, United States, division of infectious diseases,department of medicine,vanderbilt university,school of medicine,nashville,tn, United States, section of pulmonary,critical care and sleep medicine,yale school of medicine,new haven,ct, United States, division of allergy,pulmonary and critical care medicine,department of medicine,vanderbilt university,school of medicine,nashville,tn, United States, division of infectious diseases,department of medicine,vanderbilt university,school of medicine,nashville,tn,united states,department of pathology,microbiology and immunology,vanderbilt university,school of medicine,nashville,tn, United States
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Authors
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