Profile of interleukin-2 production in human mononuclear cells and T-cell lines

Document Type : Research Paper


1 Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran.

2 Department of Physiology, Faculty of Medicine, Shahed University, Tehran, Iran.


Introduction: Interleukin-2 (IL-2) as a T helper type 1 (Th1) cytokine has an important role Background and Objective: Interleukin-2 (IL-2) as a T helper type 1 (Th1) cytokine has an important role in activation, growth and differentiation of several immune cells. Moreover IL-2 is known as a pro-inflammatory and anti-tumoral cytokine. In addition deysregulation of IL-2 in some diseases such as autoimmunity has been shown. The present study was conducted to evaluate the patterns of IL-2 production in human peripheral blood mononuclear cells (PBMCs) and human leukemic T cells lines (Molt-4 and Jurkat).

Materials and Methods: Human PBMCs and leukemic T cells were cultured in complete RPMI-1640 medium. The cells were then seeded at a density of 106 cells/ml and were incubated with different concentrations of phorbol myristate acetate (PMA) (1-25 ng/ml) or phytoheamagglutinin (PHA) (2-10 μg/ml) for 48 hours. Then the cell-conditioned media were collected and used for IL-2 assay. Statistical comparisons between groups were made by analysis of variance (ANOVA).

Results: PHA/PMA significantly and dose-dependently increased IL-2 level in human PBMCs and leukemic T cells (Molt-4 and Jurkat) after 48 hours of incubation compared with untreated control cells.

Conclusion: We conclude that human PBMCs and leukemic T cells (Jurkat and Molt-4) could potentially secrete IL-2 with different degrees. Thus, these cells could offer a proper system to study the mechanisms regulating IL-2 production in diseases in which IL-2 production is disregulated. Also these cells could be useful for screening the IL-2 modulators.


1. Schett G1. Dayer JM2, Manger B1. Interleukin-1 function and role in rheumatic disease. Nature Reviews Rheumatology 2016; 12(1):14-24.
2. Tukler Henriksson J1, Coursey TG1, Corry DB2, De Paiva CS1, Pflugfelder SC1. IL-13 Stimulates Proliferation and Expression of Mucin and Immunomodulatory Genes in Cultured Conjunctival Goblet Cells 2015; 56(8):4186-97.
3. Rohm I, Ratka J, Pistulli R, Goebel B, Gecks T, Figulla HR. et al. Impact of Systemic Normobaric Short-Term Hypoxia on Pro-Inflammatory and Anti-Inflammatory Cytokines in Healthy Volunteers. Clinical Laboratory 2015; 61(8):1053-9.
4. Hu X, Cao Y, Meng Y, Hou M. A novel modulation of structural and functional changes of mouse bone marrow derived dendritic cells (BMDCs) by interleukin-2(IL-2). Human Vaccines & Immunotherapeutics 2015; 11(2):516-21.
5. Geok Choo SimaAuthor Vitae, Laszlo Radvanyia b. The IL-2 cytokine family in cancer immunotherapy. Cytokines and growth factor reviews 2014; 25(4): 377–390.
6. Das S1, Freier A, Boussoffara T, Das S, Oswald D, Losch FO. Modular multiantigen T cell epitope-enriched DNA vaccine against human leishmaniasis. Science Translational Medicine 2014; 6(234):234ra56.
7. Lee SB1, Kim YH2, Hyun MC1, Kim YH1, Kim HS3, Lee YH2. T-Helper Cytokine Profiles in Patients with Kawasaki Disease. Korean Circulation Journal 2015; 45(6):516-21.
8. Wang Z, Wang G, Zhu X, Geng D, Yang H. Interleukin-2 is upregulated in patients with a prolapsed lumbar intervertebral disc and modulates cell proliferation, apoptosis and extracellular matrix metabolism of human nucleus pulposus cells. Experimental and Therapeutic Medicine 2015; 10(6):2437-2443.
9. Varzaneh FN1, Keller B, Unger S, Aghamohammadi A, Warnatz K, Rezaei N. Cytokines in common variable immunodeficiency as signs of immune dysregulation and potential therapeutic targets - a review of the current knowledge. Journal of Clinical Immunology 2014; 34(5):524-43.
10. X. Geng R, Zhang G, Yang, W, Jiang C Xu. Interleukin-2 and autoimmune disease occurrence and therapy. European Review for Medical and Pharmacological Sciences 2012; 16 (11): 1462-1467.11. Dayakar A1, Chandrasekaran S1, Veronica J1, Maurya RS2. Leptin induces the phagocytosis and protective immune response in Leishmania donovani infected THP-1 cell line and human PBMCs. Experimental Parasitology 2016;160:54-9.
12. Kim N, Jeon YW, Nam YS, Lim JY, Im KI, Lee ES, Cho SG. Therapeutic potential of low-dose IL-2 in a chronic GVHD patient by in vivo expansion of regulatory T cells. Cytokine 2016; 78:22-26.
13. Peng XQ, Zhou HF, Lu YY, Chen JK, Wan HT, Zhang YY. Protective effects of Yinhuapinggan granule on mice with influenza viral pneumonia. International Immunopharmacology 2015; 30:85-93.
14. Yang TH, Hsu PY, Meng M, Su CC. Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-induced arthritis. Arthritis Research & Therapy 2015; 17(1):364.
15. Sarada S, Titto M, Himadri P, Saumya S, Vijayalakshmi V. Curcumin prophylaxis mitigates the incidence of hypobaric hypoxia-induced altered ion channels expression and impaired tight junction proteins integrity in rat brain. Journal of Neuroinflammation 2015; 6(12):113.
16. Lv QK1, Liu JX2, Li SN3, Gao YJ4, Lv Y5, Xu ZP6, etal. Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model. International Journal of Molecular Sciences. 2015; 16(11):26654-66.
17. Zhu Y, Li X, Chen J, Chen T, Shi Z, Lei M, et al. The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease. International Immunopharmacology. 2015;30:74-84
18. Gao Y1, Kang L, Li C, Wang X, Sun C, Li Q, et al. Resveratrol Ameliorates Diabetes-Induced Cardiac Dysfunction Through AT1R-ERK/p38 MAPK Signaling Pathway. Cardiovascular Toxicology. 2016; 16(2):130-137.
19. Hajighasemi F, Hajighasemi S. Effect of propranolol on angiogenic Factors in Human Hematopoietic Cell Lines in vitro. Iranian Biomedical. Journal 2009; 13: 157-162.
20. Sung SS, Jung LK, Walters JA, Chen W, Wang CY, Fu SM. Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells. Journal of Experimental Medicine 1988; 168(5):1539-51.
21. Severino L1, Luongo D, Bergamo P, Lucisano A, Rossi M. Mycotoxins nivalenol and deoxynivalenol differentially modulate cytokine mRNA expression in Jurkat T cells. Cytokine 2006; 36(1-2):75-82.
22. Khan FA1, Al-Jameil N1, Khan MF1, Al-Rashid M1, Tabassum H1. Thyroid dysfunction: an autoimmune aspect. International Journal of Clinical and Experimental Medicine 2015; 8(5):6677-81.
23. Turhan Iyidir O1, Konca Degertekin C2, Sonmez C3, Atak Yucel A3, Erdem M4, Akturk M2, Ayvaz G2.The effect of thyroid autoimmunity on T-cell responses in early pregnancy. Journal of Reproductive
Immunology 2015; 110:61-6.
24. Pérol L, Piaggio E. New Molecular and Cellular Mechanisms of Tolerance: Tolerogenic Actions of IL-2. Methods in molecular
biology 2016; 1371:11-28.
25. Dutta A, Banerjee A, Saikia N, Phookan J, Baruah MN, Baruah S. Negative regulation of natural killer cell in tumor tissue and peripheral blood of oral squamous cell carcinoma. Cytokine 2015; 76(2):123-30.
26. Fuchs S1, Rensing-Ehl A2, Pannicke U3, Lorenz MR3, Fisch P4, Jeelall Y5 . Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency. Blood 2015; 126(14):1658-69.
27. Zhang B, Qiu J, Wu C, Li Y, Liu Z. Anti-tumor and immunomodulatory activity of iron hepta-tungsten phosphate oxygen clusters complex. International Immunopharmacology 2015; 29(2):293-301.
28. Mao GH, Ren Y, Li Q, Wu HY, Jin D, Zhao T etal. Anti-tumor and immunomodulatory activity of selenium (Se)-polysaccharide from Se-enriched Grifola frondosa. International Journal of Biological Macromolecules 2016; 82:607-13.
29. Li W, Xu Q, He YF, Liu Y, Yang SB, Wang Z, et al. Anti-Tumor Effect of Steamed Codonopsis lanceolata in H22 Tumor-Bearing Mice and Its Possible Mechanism. Nutrients 2015; 7(10):8294-8307.
30. Kevin R. Mott, Mandana Zandian, Sariah J. Allen, Homayon Ghiasi.
31. Role of Interleukin-2 and Herpes Simplex Virus 1 in Central Nervous System Demyelination in Mice. Journal of Virology 2013; 87(22): 12102–12109.
32. Wei Liao, Jian-Xin Lin, Warren J. Leonard. Interleukin-2 at the Crossroads of Effector Responses, Tolerance, and Immunotherapy. Immunity 2013; 38(1): 13–25.
33. Zhang M1, Mathews Griner LA2, Ju W3, Duveau DY2, Guha R2. Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2-dependent adult T-cell leukemia. Proceedings of the National Academy of Sciences 2015;112(40):12480-5.
34. Tobin NP1, Foukakis T1, De Petris L1, Bergh J. The importance of molecular markers for diagnosis and selection of targeted treatments in patients with cancer. Journal of Internal Medicine 2015 Dec;278(6):545-70.
35. Kucera R1, Topolcan O1, Treskova I2, Kinkorova J3, Windrichova J1, Fuchsova R1. Evaluation of IL-2, IL-6, IL-8 and IL-10 in Malignant Melanoma Diagnostics. Anticancer Research 2015; 35(6):3537-41.
36. Mora DJ1, Fortunato LR1, Andrade-Silva LE1, Ferreira-Paim K1, Rocha IH1, Vasconcelos RR. Cytokine profiles at admission can be related to outcome in AIDS patients with cryptococcal meningitis. PLoS One 2015, 23; 10(3):e0120297.
37. Bayhan Z, Simşek T, Ergül E, Utkan NZ, Canturk NZ, Cekmen M. Serum cytokine levels in patients with colorectal cancers according to tumor stages and VEGF gene polymorphism. Hepatogastroenterology 2014; 61(135):1889-94.
38. Minciullo PL, Catalano A, Mandraffino G, Casciaro M, Crucitti A, Maltese G. Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity. Archivum Immunologiae et Therapia Experimentalis 2016; 64(2):111-26.
39. Hellinger R1, Koehbach J1, Fedchuk H2, Sauer B2, Huber R2, Gruber CW1, Gründemann C. Immunosuppressive activity of an aqueous Viola tricolor herbal extract. Journal of Ethnopharmacol 2014; 151(1):299-306.
40. Hajighasemi F, Mirshafiey A. In vitro effects of propranolol on T helper type 1 cytokine profile in human leukemic T cells. International Journal of Hematology- Oncology and Stem Cell Research 2016; 10(2): 131-137.