NK Cells in Sarcoidosis

Abstract

To the Editor: Diagnostic bronchoalveolar lavage (BAL), with the determination and enumeration of the recovered nucleated cells, has gained wide acceptance in the evaluation of alveolar and interstitial pulmonary diseases.1Crystal RG Reynold HY Kalica AR Bronchoalveolar lavage. The report of an international conference.Chest. 1986; 90: 122-131Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar Evolutive sarcoidosis, for example, is characterized by the exudation of activated T-helper cells. Recently we have had the opportunity to observe an unusual increase in NK cells, the “third” or “null” lymphocyte subpopulation, in an aged patient with sarcoidosis. An 80-year-old Caucasian woman was admitted because of mental deterioration and confusion. No specific complaint was elicited. Fine crackling pulmonary rales were heard at both bases. The biology was unremarkable; acute phase reactants, serum calcium, alkaline phosphatase, gamma-glutamyl transferase and angiotensin converting enzyme were normal. Gammaglobulins were mildly depressed at 630 mg/L. Routine chest x-ray and computed tomographic examinations disclosed hilar adenopathies and a mild bibasilar fibrosis. Functional respiratory tests could not be performed. As shown in Table 1, NK cells as determined by anti-CD16 monoclonal antibodies2Lanier LL Le AM Phillips JH Warner NL Babcock GF Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens.J Immunol. 1983; 131: 1789-1796PubMed Google Scholar, 3Ligthart GJ Van Vlokhoven PC Schuit HRE Hijmans W The expanded null cell compartment in aging: increase in the number of natural killer cells and changes in T-cell and NK-cell subsets in human blood.Immunology. 1986; 59: 353-357PubMed Google Scholar were markedly increased in BAL and marginally in peripheral blood. Bronchial biopsy was negative. Multiple adenopathies were observed at mediastinoscopy, and histology revealed typical noncaseating granulomas.Table 1Cell Subpopulations in Peripheral Blood (PB), Ficoll-Paque Isolated Mononuclear Cells (PBMC) and Bronchoalveolar Liquid (BAL) in an Aged Patient with Silent Sarcoidosis.PBPBMCBALcell count/µl9100314percentage of neutrophils602 lymphocytes196 lymphocytesmonocytes1050 lymphocytesimmunofluorescent subsets %PredominantMoAbSpecificityreactivityOKT3CD3pan-T448OKT4CD4TH202OKT8CD8TS/C216Leu 11CD16NK2335OKM1CR3-CD11NK, PMN, mono2511OKM3—mono4468OKIamonomorphic HLA-DRB, mono, activated T3821Leu 16CD20B81 Open table in a new tab In normal people, NK cells are very few in BAL samples.4Costabel U Bross KJ Reuter C Rühle KH Mathys H Alterations in immunoregulatory T-cell subsets in cigarette smokers.A phenotypic analysis of bronchoalveolar and blood lymphocytes. Chest. 1986; 90: 39-44Google Scholar Our experience in diseased patients is limited, but NK cells did not exceed 12 percent (n = 6, m = 3.8, range 0 to 12). In our patients, 63,740 NK cells/ml of BAL fluid were found. Great care must be exercised in generalizing the data from a single case. However, it raises fruitful hypotheses. NK cell infiltration could be the hallmark of sarcoidosis in old age, the more so as the null cell compartment is expanded in aging.3Ligthart GJ Van Vlokhoven PC Schuit HRE Hijmans W The expanded null cell compartment in aging: increase in the number of natural killer cells and changes in T-cell and NK-cell subsets in human blood.Immunology. 1986; 59: 353-357PubMed Google Scholar Alternatively, NK increase in BAL could probe quiescent pulmonary sarcoidosis, the clinical picture in our patient. Indeed, NK cells exert suppressive effects on T and B lymphocytes.5Ferrarini M Grossi CE Definition of the cell types within the “null lymphocyte” population of human peripheral blood: an analysis of phenotypes and functions.Hematol. 1984; 21: 270-281Google Scholar In the present case, the association of sarcoidosis with NK cells could have been coincidental. However, no explanation can be found. Our patient did not display any symptoms of another disease, such as acute viral disease or leukemoid NK lymphocytosis.5Ferrarini M Grossi CE Definition of the cell types within the “null lymphocyte” population of human peripheral blood: an analysis of phenotypes and functions.Hematol. 1984; 21: 270-281Google Scholar Sarcoid-like granulomas are often observed in voisinage of tumoral foci, but neoplasia is more frequently associated with NK depression.5Ferrarini M Grossi CE Definition of the cell types within the “null lymphocyte” population of human peripheral blood: an analysis of phenotypes and functions.Hematol. 1984; 21: 270-281Google Scholar Determination of the NK subset in BAL clearly deserves further studies in pulmonary diseases.