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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<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cells demonstrated reductions in Th1 cytokine expression, proliferative capacity (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:math>), enhanced apoptosis (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.01<\/mml:mn><\/mml:math>), and increased PD-1 expression (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.001<\/mml:mn><\/mml:math>). BAL-derived CD4<jats:sup>+<\/jats:sup> T cells also demonstrated multiple facets of T cell exhaustion (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:math>). Reversal of CD4<jats:sup>+<\/jats:sup> T cell exhaustion was observed in subjects undergoing spontaneous resolution (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:math>). Sarcoidosis CD4<jats:sup>+<\/jats:sup> T cells exhibit loss of cellular function during progressive disease that follows the archetype of T cell exhaustion.<\/jats:p>","DOI":"10.1155\/2017\/3642832","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T18:31:46Z","timestamp":1509993106000},"page":"1-14","source":"Crossref","is-referenced-by-count":34,"title":["Local and Systemic CD4<sup>+<\/sup> T Cell Exhaustion Reverses with Clinical Resolution of Pulmonary Sarcoidosis"],"prefix":"10.1155","volume":"2017","author":[{"given":"Charlene","family":"Hawkins","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guzel","family":"Shaginurova","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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