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 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.