Pulmonary Sarcoidosis: A Disorder Mediated by Excess Helper T-Lymphocyte Activity at Sites of Disease Activity

Gary W. Hunninghake, Ronald Crystal

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Abstract

Using the monoclonal antibodies OKT4 and OKT8, we determined the proportions of helper and suppressor T cells in patients with sarcoidosis and high-intensity alveolitis, patients with sarcoidosis and low-intensity alveolitis, patients with idiopathic pulmonary fibrosis (IPF), and normal controls. In controls and patients with IPF, the ratio of helper to suppressor T cells was 1.8:1 in lungs and blood. In contrast, this ratio was 10.5:1 in lungs (P<0.001) and 0.8:1 in blood (P<0.05) in patients with sarcoidosis and high-intensity alveolitis. The ratio of helper to suppressor T cells was not higher in the lungs or blood of patients with sarcoidosis and low-intensity alveolitis; on the contrary, because of the higher proportions of suppressor cells, the ratio of helper to suppressor cells was lower in both lungs and blood. In studies of function, lung T cells from patients with sarcoidosis and high-intensity alveolitis released monocyte chemotactic factor (a lymphokine critical to granuloma formation) and polyclonally activated B cells to produce immunoglobulins. We conclude that one determinant of lung injury in sarcoidosis is the presence of large numbers of lung helper T cells, which are important in granuloma formation. (N Engl J Med. 1981; 305:429–34.). PULMONARY sarcoidosis is a chronic interstitial lung disease characterized by granulomas in the alveolar structures1 2 3 4 5 6 7 8 9 and a polyclonal hypergammaglobulinemia.10 11 12 13 14 15 16 17 Prior studies have demonstrated that both granuloma formation and local antibody production are modulated by activated lung T lymphocytes in patients with active disease (i.e., those with high-intensity alveolitis).4,5,16,17 In this regard, lung T cells from patients with high-intensity alveolitis spontaneously release a variety of lymphokines, including monocyte chemotactic factor, which attracts blood monocytes, the “building blocks” of granulomas, to the alveolar structures.5 In addition, these lung T cells polyclonally activate B cells to differentiate into immunoglobulin-secreting cells.16 In contrast to. . .

Original languageEnglish
Pages (from-to)429-434
Number of pages6
JournalNew England Journal of Medicine
Volume305
Issue number8
DOIs
Publication statusPublished - 20 Aug 1981
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

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