Background: Eosinophilic lung diseases comprise a group of heterogeneous pulmonary disorders linked by increased eosinophils in bronchoalveolar lavage fluid (BALF). There is supporting evidence that natural killer (NK) cells participate in the regulation of eosinophilic inflammation. Objective: Our aim was to investigate the relationship between eosinophils and NK cells in BALF in patients with different interstitial lung diseases (ILDs) focusing on eosinophilic pneumonias. Methods: Of 114 patients who presented with increased BALF eosinophils (>5%), 74 patients were classified into the following groups: 27 had eosinophilic pneumonia (EP), 17 had idiopathic pulmonary fibrosis (IPF), 16 had hypersensitivity pneumonitis (HSP) and 14 had cryptogenic organizing pneumonia (COP/BOOP). Total BALF cells, cell density and cell differential counts were assessed and lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3–CD16/56+ (NK) and CD3+CD16/56+ (NKT) were determined by flow cytometry. Results: Significant differences were observed in the percentages of lymphocytes (p < 0.001) and CD3+CD16/56+ cells (p = 0.023) among patient groups. In patients with EP, the percentage of eosinophils correlated positively with the number of CD3–CD16/56+ cells (r = 0.522, p = 0.005), the percentage of CD3–CD16/56+ cells (r = 0.690, p < 0.001), and the absolute count of CD3+CD16/56+ absolute cells (r = 0.609, p = 0.001). However, in patients with IPF, HSP or COP/BOOP, no correlation between the percentage of eosinophils and CD3–CD16/56+ or CD3+CD16/56+ cells was observed. Conclusions: Eosinophil inflammation seems to develop through a different pathway in EP compared to other ILDs.

Keywords:
Eosinophils, Eosinophilic pneumonias, Bronchoalveolar lavage fluid, Interstitial lung diseases, CD3–CD16/56+ cells, CD3+CD16/56+cells
1.
Klech H, Pohl W: Clinical guidelines and indications for bronchoalveolar lavage (BAL): report of the European Society of Pneumonology Task Force on BAL. Eur Respir J 1990;3:937–974.
2.
Costabel U, Guzman J: Bronchoalveolar lavage in interstitial lung disease. Curr Opin Pulm Med 2001;7:255–261.
3.
Allen JN, Davis WB, Pacht ER: Diagnostic significance of increased bronchoalveolar lavage fluid eosinophils. Am Rev Respir Dis 1990;142:642–647.
4.
Walker C, Bauer W, Braun RK, Menz G, Braun P, Schwarz F, Hansel TT, Villiger B: Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med 1994;150:1038–1048.
5.
Taniguchi H, Kadota J, Fujii T, Matsubara Y, Katoh S, Mukae H, Matsukura S, Kohno S: Activation of lymphocytes and increased interleukin-5 levels in bronchoalveolar lavage fluid in acute eosinophilic pneumonia. Eur Respir J 1999;13:217–220.
6.
Azuma M, Nakamura Y, Sano T, Okano Y, Sone S: Adhesion molecule expression on eosinophils in idiopathic eosinophilic pneumonia. Eur Respir J 1996;12:2494–2500.
7.
Korsgren M, Persson CG, Sundler F, Bjerke T, Hansson T, Chambers BJ, Hong S, Van Kaer L, Ljunggren HG, Korsgren O: Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice. J Exp Med 1999;189:553–562.
8.
Bilenki L, Yang J, Fan Y, Wang S, Yang X: Natural killer T cells contribute to airway eosinophilic inflammation induced by ragweed through enhanced IL-4 and eotaxin production. Eur J Immunol 2004;34:345–354.
9.
Kim JO, Kim DH, Chang WS, Hong C, Park SH, Kim S, Kang CY: Asthma is induced by intranasal coadministration of allergen and natural killer T-cell lingand in a mouse model. J Allergy Clin Immunol 2004;114:1332–1338.
10.
Message SD, Johnston SL: The immunology of virus infection in asthma. Eur Respir J 2001;18:1013–1025.
11.
Timonen T, Stenious B: Natural killer cell activity in asthma. Clin Exp Immunol 1985;59:85–90.
12.
Morishima Y, Ishii Y, Kimura T, Shibuya K, Hegab AE, Iizuka T, Kiwamoto T, Matsuno Y, Sakamoto T, Nomura A, Taniguchi M, Sekizawa K: Suppression of eosinophilic airway inflammation by treatment with α-galactosylceramide. Eur J Immunol 2005;35:2803–2814.
13.
Tomura M, Yu WG, Ahn HJ, Yamashita M, Ono S, Hamaoka T, Kawano T, Taniguchi M, Koezuka Y, Fujiwara H: A novel function of Vα14+CD4+NKT cells: stimulation pf IL-12 production by antigen-presenting cells in the innate immune system. J Immunol 1999;163:93–101.
14.
Otani T, Nakamura S, Toki M, Motoda R, Kurimoto M, Orita K: Identification of IFN-γ producing cells in IL-12/IL-18-treated mice. Cell Immunol 1999;198:111–119.
15.
Allen JN, Davis WB: Eosinophilic lung diseases. Am J Respir Crit Care Med 1994;150:1423–1438.
16.
Carrington CB, Addington WW, Golf AM, Madoff IM, Marks A, Schwaber JR, Gaensler EA: Chronic eosinophilic pneumonia. N Engl J Med 1969;280:787–798.
17.
American Thoracic Society, European Respiratory Society: Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med 2000;161:646–664.
18.
Lacasse Y, Selman M, Costabel U, Dalphin JC, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, Cormier Y, HP Study Group: Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med 2003;168:952–958.
19.
American Thoracic Society, European Respiratory Society: International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med 2002;165:277–304.
20.
Welker L, Jorres RA, Costabel U, Magnussen H: Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases. Eur Respir J 2004;24:1000–1006.
21.
Velay B, Pages J, Cordier JF, Brune J: Hyperéosinophilie du lavage broncho-alvéolaire: valeur diagnostique et corrélation avec l’éosinophilie sanguine. Rev Mal Respir 1987;4:257–260.
22.
Olivieri D, Pecsi A, Bertorelli G: Eosinophilic alveolitis in immunologic interstitial disorders. Lung 1990;168:964–973.
23.
Marchand E, Reynaud-Gaubert M, Lauque D, Durieu J, Tonnel AB, Cordier JF: Idiopathic chronic eosinophilic pneumonia: a clinical and follow-up study of 62 cases. Medicine (Baltimore) 1998;77:299–312.
24.
Veeraraghavan S, Latsi PI, Wells AU, Pantelidis P, Nicholson AG, Colby TV, Haslam PL, Rezoni EA, du Bois RMl: BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia. Eur Respir J 2003;22:239–244.
25.
Haslam PL, Poulter LW, Rossi GA, Bauer W, De Rose V, Eckert H, Olivieri D, Teschler H: The clinical role of BAL in idiopathic pulmonary fibrosis. Eur Respir J 1990;3:940–942, 961–969.
26.
Drent M, Wagenaar SS, van Velzen-Blad H, Mulder PG, Hoogsteden HC, Van den Bosch JM: Relationship between plasma cell levels and profile of bronchoalveolar lavage fluid in patients with subacute extrinsic allergic alveolitis. Thorax 1993;48:835–839.
27.
Albera C, Ghio P: Eosinophils in eosinophilic pneumonia. Eur Respir J 1996;9:2437–2439.
28.
Albera C, Ghio P, Solidoro P, Mabritto I, Marchetti L, Pozzi E: Activated and memory alveolar T-lymphocytes in idiopathic eosinophilic pneumonia. Eur Respir J 1995;8:1281–1285.
29.
Katoh S, Fukushima K, Matsumoto N, Matsumoto K, Abe K, Onai N, Matsushima K, Matsukura S: Accumulation of CCR4-expressing CD4+ T cells and high concentration of its lingands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. Allergy 2003;58:518–523.
30.
Izumi T, Kitaichi M, Nishimura K, Nagai S: Bronchiolitis obliterans organizing pneumonia: clinical features and differential diagnosis. Chest 1992;102:715–719.
31.
Fujimura M, Yasui M, Shinagawa S, Nomura M, Matsuda T: Bronchoalveolar lavage cell findings in three types of eosinophilic pneumonia: acute, chronic and drug-induced eosinophilic pneumonia. Respir Med 1998;92:743–749.
32.
Mukae H, Kadota J, Kohno S, Matsukura S, Hara K: Increase of activated T-cells in BAL fluid of Japanese patients with bronchiol- itis obliterans organizing pneumonia and chronic eosinophilic pneumonia. Chest 1995;108:123–128.
33.
Papakosta D, Manika K, Kyriazis G, Kontakiotis T, Manolakoglou N, Gioulekas D, Bouros D, Patakas D: Comparison of alveolar cell populations, NK and NKT cells between COP/BOOP and eosinophilic pneumonia. Abstr 10th Int Conf BAL, Coimbra, 2006, p 60.
34.
Korosec P, Osolnik K, Kern I, Silar M, Mohorcic K, Kosnik M: Expansion of pulmonary CD8+CD57+ natural killer T-cells in hypersensitivity pneumonitis. Chest 2007;132:1291–1297.
35.
Weissler JC, Nicod LP, Lipscomb MF, Toews GB: Natural killer cell function in human lung is compartmentalized. Am Rev Respir Dis 1987;135:941–949.
36.
Lasek WA, Plodziszewska M, Gorechki D, Jakobisiak M: Relationship between natural killer (NK) activity and eosinophil, neutrophil and lymphocyte level in human blood. Folia Haematol Int Mag Klin Morphol Blutforsch 1985;112:907–912.
37.
Walker C, Checkel J, Cammisuli S, Leibson PJ, Gleich GJ: IL-5 production by NK cells contributes to eosinophil infiltration in a mouse model of allergic inflammation. J Immunol 1998;161:1962–1969.
38.
Kobayashi S, Kaneko Y, Seino K, Yamada Y, Motohashi S, Koike J, Sugaya K, Kuriyama, T Asano S, Tsuda T, Wakao H, Harada M, Kojo S, Nakayama T, Taniguchi M: Impaired INF-γ production of Valpha 24 NKT cells in non-remitting sarcoidosis. Int Immunol 2004;16:215–222.
39.
Papakosta D, Kyriazis G, Gioulekas D, Kontakiotis T, Polyzoni T, Bouros D, Patakas D: Variations in alveolar cell populations, lymphocyte subsets and NK-cells in different stages of active pulmonary sarcoidosis. Sarc Vasc Diffuse Lung Dis 2005;22:21–26.
40.
Katchar K, Soderstrom K, Wahlstrom J, Eklund A, Grunewald J: Characterization of natural killer cells and CD56+ T-cells in sarcoidosis patients. Eur Respir J 2005;26:77–85.
41.
Lisbonne M, Diem S, de Castro Keller A, Lefort J, Araujo LM, Hachem P, Fourneau JM, Sidobre S, Kronenberg M, Taniguchi M, Van Endert P, Dy M, Askenase P, Russo M, Vargaftig BB, Herbelin A, Leite-de-Moraes MC: Cutting edge: invariant Vα 14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model. J Immunol 2003;171:1637–1641.
42.
Ikegami Y, Yokoyama A, Haruta Y, Hiyama K, Kohno N: Circulating natural killer T cells in patients with asthma. J Asthma 2004;41:877–882.
43.
Meyer EH, Goya S, Akbari O, Berry GJ, Savage PB, Kronenberg M, Nakayama T, DeKruyff RH, Umetsu DT: Glycolipid activation of invariant T cell receptor + NKT cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc Natl Acad Sci USA 2006;103:2782–2787.
44.
Thornton AM, Shevach EM: CD25+CD4+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998;188:287–296.
45.
Kursar M, Bonhagen K, Fensterle J, Kohler A, Hurwitz R, Kamradt T, Kaufmann SH, Mittrucker HW: Regulatory CD25+CD4+ T cells restrict CD8+ T cell responses. J Exp Med 2002;196:1585–1592.
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