Main Article Content
Bronchoalveolar lavage, Lymphocytes, Natural killer cells, Natural killer T-like cells, Sarcoidosis
Background and objective: Data on natural killer (NK)- and natural killer T (NKT)- like cells in the immunopathogenesis of sarcoidosis remain limited. The aim was to assess NK- and NKT-like cells across different stages in bronchoalveolar lavage (BALF) versus peripheral blood (PB) in comparison to controls.
Methods: Forty four patients (32 women and 12 men, mean age 46.6±14.4 years) with biopsy-proven sarcoidosis and 10 healthy individuals (6 women, 4 men mean age 52.6±19.1 years) were submitted to BALF. Total cells and cell differentials were counted, while CD45+, CD3+, CD4+, CD8+, CD19+, CD3-CD16/56 (NK cells) and CD3+CD16/56+ (NKT-like cells) were determined by dual flow cytometry in BALF and PB.
Results: A significantly lower percentage of both NK and NKT-like cells was observed in BALF of controls and sarcoid patients (SP) compared to PB. Both BALF NK and NKT-cell counts were significantly higher in SP than in controls (NK: p=0.046, NKT-like: p=0.012) In addition BALF NK cell percentage differed among sarcoidosis stages (p=0.005). In PB NK-cell count was lower in sarcoidosis patients but the difference did not reach statistical significance. Also, in sarcoid patients’ BALF NK-cell percentage negatively correlated with lymphocyte percentage (r=-0.962, p<0.001).
Conclusions: The increased count of BALF NK and NKT-like cells in sarcoidosis compared to controls along with the increase of NK cells with stage progression are in line with a growing number of investigations suggesting the involvement of NK- and NKT-like cells in the pathogenesis of sarcoidosis.
2. Noor A, Knox KS. Immunopathogenesis of sarcoidosis. Clin Dermatol. 2007;25(3):250-8.
3. Zissel G, Prasse A, Muller-Quernheim J. Immunologic response of sarcoidosis. Semin Respir Crit Care Med. 2010;31(4):390-403.
4. Cinetto F, Agostini C. Advances in understanding the immunopathology of sarcoidosis and implications on therapy. Expert Rev Clin Immunol. 2016;12(9):973-88.
5. Korosec P, Rijavec M, Silar M, Kern I, Kosnik M, Osolnik K. Deficiency of pulmonary Valpha24 Vbeta11 natural killer T cells in corticosteroid-naive sarcoidosis patients. Respir Med. 2010;104(4):571-7.
6. Sokhatska O, Padrao E, Sousa-Pinto B, Beltrao M, Mota PC, Melo N, et al. NK and NKT cells in the diagnosis of diffuse lung diseases presenting with a lymphocytic alveolitis. BMC Pulm Med. 2019;19(1):39.
7. Bergantini L, Cameli P, d'Alessandro M, Vagaggini C, Refini RM, Landi C, et al. NK and NKT-like cells in granulomatous and fibrotic lung diseases. Clin Exp Med. 2019;19(4):487-94.
8. Ksienzyk A, Neumann B, Nandakumar R, Finsterbusch K, Grashoff M, Zawatzky R, et al. IRF-1 expression is essential for natural killer cells to suppress metastasis. Cancer Res. 2011;71(20):6410-8.
9. Li F, Zhu H, Sun R, Wei H, Tian Z. Natural killer cells are involved in acute lung immune injury caused by respiratory syncytial virus infection. J Virol. 2012;86(4):2251-8.
10. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503-10.
11. Rijavec M, Volarevic S, Osolnik K, Kosnik M, Korosec P. Natural killer T cells in pulmonary disorders. Respir Med. 2011;105 Suppl 1:S20-5.
12. Godfrey DI, Stankovic S, Baxter AG. Raising the NKT cell family. Nat Immunol. 2010;11(3):197-206.
13. Van Kaer L, Parekh VV, Wu L. Invariant natural killer T cells: bridging innate and adaptive immunity. Cell Tissue Res. 2011;343(1):43-55.
14. Papakosta D, Manika K, Kyriazis G, Kontakiotis T, Gioulekas D, Polyzoni T, et al. Bronchoalveolar lavage fluid eosinophils are correlated to natural killer cells in eosinophilic pneumonias. Respiration. 2009;78(2):177-84.
15. Korosec P, Osolnik K, Kern I, Silar M, Mohorcic K, Kosnik M. Expansion of pulmonary CD8+CD56+ natural killer T-cells in hypersensitivity pneumonitis. Chest. 2007;132(4):1291-7.
16. Segawa S, Goto D, Yoshiga Y, Horikoshi M, Sugihara M, Hayashi T, et al. Involvement of NK 1.1-positive gammadeltaT cells in interleukin-18 plus interleukin-2-induced interstitial lung disease. Am J Respir Cell Mol Biol. 2011;45(3):659-66.
17. Tondell A, Ro AD, Asberg A, Borset M, Moen T, Sue-Chu M. Activated CD8(+) T cells and NKT cells in BAL fluid improve diagnostic accuracy in sarcoidosis. Lung. 2014;192(1):133-40.
18. Papakosta D, Kyriazis G, Gioulekas D, Kontakiotis T, Polyzoni T, Bouros D, et al. Variations in alveolar cell populations, lymphocyte subsets and NK-cells in different stages of active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2005;22(1):21-6.
19. Technical recommendations and guidelines for bronchoalveolar lavage (BAL). Report of the European Society of Pneumology Task Group. Eur Respir J. 1989;2(6):561-85.
20. Meyer KC, Raghu G, Baughman RP, Brown KK, Costabel U, du Bois RM, et al. An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med. 2012;185(9):1004-14.
21. Tutor-Ureta P, Citores MJ, Castejon R, Mellor-Pita S, Yebra-Bango M, Romero Y, et al. Prognostic value of neutrophils and NK cells in bronchoalveolar lavage of sarcoidosis. Cytometry B Clin Cytom. 2006;70(6):416-22.
22. Liu DH, Cui W, Chen Q, Huang CM. Can circulating interleukin-18 differentiate between sarcoidosis and idiopathic pulmonary fibrosis? Scand J Clin Lab Invest. 2011;71(7):593-7.
23. Sakthivel P, Bruder D. Mechanism of granuloma formation in sarcoidosis. Curr Opin Hematol. 2017;24(1):59-65.
24. Ocal N, Dogan D, Ocal R, Tozkoparan E, Deniz O, Ucar E, et al. Effects of radiological extent on neutrophil/lymphocyte ratio in pulmonary sarcoidosis. Eur Rev Med Pharmacol Sci. 2016;20(4):709-14.
25. Agostini C, Semenzato G, Zambello R, Trentin L, Luca M, Cipriani A, et al. Impaired production of interleukin-2 in peripheral blood of patients with sarcoidosis. Boll Ist Sieroter Milan. 1985;64(3):226-31.
26. Kopinski P, Przybylski G, Jarzemska A, Sladek K, Soja J, Iwaniec T, et al. [Interferon gamma (IFN-gamma) level in broncholaveolar lavage (BAL) fluid is positively correlated with CD4/CD8 ratio in selected interstitial lung diseases]. Pol Merkur Lekarski. 2007;23(133):15-21.
27. Katchar K, Soderstrom K, Wahlstrom J, Eklund A, Grunewald J. Characterisation of natural killer cells and CD56+ T-cells in sarcoidosis patients. Eur Respir J. 2005;26(1):77-85.
28. Ho LP, Urban BC, Thickett DR, Davies RJ, McMichael AJ. Deficiency of a subset of T-cells with immunoregulatory properties in sarcoidosis. Lancet. 2005;365(9464):1062-72.
29. Mempel M, Flageul B, Suarez F, Ronet C, Dubertret L, Kourilsky P, et al. Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly biased T cell receptor Valpha repertoire. Am J Pathol. 2000;157(2):509-23.
30. Kobayashi S, Kaneko Y, Seino K, Yamada Y, Motohashi S, Koike J, et al. Impaired IFN-gamma production of Valpha24 NKT cells in non-remitting sarcoidosis. Int Immunol. 2004;16(2):215-22.
31. Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlstrom J, Kronenberg M, et al. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med. 2006;354(11):1117-29.