CD4+CD28- T cells are expanded in sarcoidosis

Background and aim: A subset of CD4+ lymphocytes lacking CD28, an important costimulatory molecule, is increased in certain inflammatory conditions. However, studies have not directly studied CD4+CD28-lymphocytes in patients with chronic sarcoidosis. The aim of this study was to further characterize the CD4+CD28-T cell population in patients with sarcoidosis, particularly those with active disease. Methods: Seventeen patients with chronic sarcoidosis and 15 blood donors were studied. Bronchoalveolar lavage cells were available for paired analysis in seven sarcoid patients. In 4 sarcoid patients, adequate sample was available for intracellular cytokine analysis by flow cytometry. IFN-γ production in plasma and BAL was determined by ELISA and cytometric bead array analysis and compared to previously studied controls. Results: Peripheral blood from patients with sarcoidosis had a significantly higher proportion of CD4+CD28-cells compared with healthy donors. A higher percentage of CD4+CD28-cells was evident in the BAL relative to peripheral blood in patients with active sarcoid. IFN-γ levels were greater both in the plasma and concentrated BAL fluid of sarcoid subjects compared to controls. The majority of IFN-γ and TNF-α producing lymphocytes were CD28+ in both healthy blood donors and sarcoid subjects. Conclusions: CD4+CD28-cells are increased in the peripheral blood and lungs of patients with sarcoidosis requiring treatment. These cells may contribute to the inflammatory response; however, they are not major contributors of IFN-γ or TNF-α.