AJMB  Vol.5 No.3 , July 2015
Inhibition of T Cell and Stimulation of B Cell Proliferation by Restraint Stress Mediated by Voltage-Gated Potassium Channel 1.3 Expression
Abstract: Our previous study has showed that restraint stress inhibits T cell proliferation. Kv1.3 plays a key role in the lymphocyte activation process. Here, we investigate the effects of restraint stress on murine splenic T and B cell proliferation and the role of Kv1.3 in the process. 3H-TdR incorporation is used to determine changes in splenocyte proliferation stimulated by Con A or LPS between control and restraint stress groups. The data shows that restraint stress inhibits T cell and enhanced B cell proliferation. Data from RT-PCR and Western blotting shows that Kv1.3 gene and protein levels are downregulated in T cells and upregulated in B cells in stressed mice. To examine a possible cause-and-effect relationship between Kv1.3 and stress-affected lymphocyte proliferation, we employ various Kv1.3 specific blockers (quinine, 4-AP and TEA) to determine K+ channel function under restraint stress. The data shows that Kv1.3 blockers reverse the decreased T cell proliferation and increase B cell proliferation induced by restraint stress. These results indicate that Kv1.3 mediates restraint stress-induced modulation of T/B lymphocyte proliferation.
Cite this paper: Feng, J. , Wang, S. and Song, D. (2015) Inhibition of T Cell and Stimulation of B Cell Proliferation by Restraint Stress Mediated by Voltage-Gated Potassium Channel 1.3 Expression. American Journal of Molecular Biology, 5, 94-104. doi: 10.4236/ajmb.2015.53008.

[1]   Ader, R. and Cohen, N. (1993) Psychoneuroimmunology: Conditioning and Stress. Annual Review of Psychology, 44, 53-85.

[2]   Zhang, Y., Zhang, Y., Miao, J.Y., Hanley, G., Stuart, C., Sun, X.L., Chen, T.T. and Yin, D.L. (2008) Chronic Restraint Stress Promotes Immune Suppression through Toll-Like Receptor 4-Mediated Phosphoinositide 3-Kinase Signaling. Journal of Neuroimmunology, 204, 13-19.

[3]   Padgett, D.A. and Glaser, R. (2003) How Stress Influences the Immune Response. Trends in Immunology, 24, 444-448.

[4]   Vig, R.S., Forsythe, P. and Vliagoftis, H. (2006) The Role of Stress in Asthma: Insight from Studies on the Effect of Acute and Chronic Stressors in Models of Airway Inflammation. Annals of the New York Academy of Sciences, 1088, 65-77.

[5]   Mahanti, S., Majhi, A., Chongdar, S., Kundu, K., Dutta, K., Basu, A. and Bishayi, B. (2012) Increased Resistance of Immobilized-Stressed Mice to Infection: Correlation with Behavioral Alterations. Brain, Behavior, and Immunity, 28, 115-127.

[6]   Katz, D.A., Sprang, G. and Cooke, C. (2012) The Cost of Chronic Stress in Childhood: Understanding and Applying the Concept of Allostatic Load. Psychodyn Psychiatry, 40, 469-480.

[7]   Reiche, E.M., Nunes, S.O. and Morimoto, H.K. (2004) Stress, Depression, the Immune System, and Cancer. The Lancet Oncology, 5, 617-625.

[8]   Kawasaki, T., Ogata, M., Kawasaki, C., Okamoto, K. and Sata, T. (2007) Effects of Epidural Anaesthesia on Surgical Stress-Induced Immunosuppression during Upper Abdominal Surgery. British Journal of Anaesthesia, 98, 196-203.

[9]   Fan, S.G., Shao, L. and Ding, G.F. (1996) A Suppressive Protein Generated in Peripheral Lymph Tissue Induced by Restraint Stress. Advances in Neuroimmunology, 6, 279-288.

[10]   Panayi, G.S., Corrigall, V.M. and Henderson, B. (2004) Stress Cytokines: Pivotal Proteins in Immune Regulatory Networks; Opinion. Current Opinion in Immunology, 16, 531-534.

[11]   Ben-Eliyahu, S. (2003) The Promotion of Tumor Metastasis by Surgery and Stress: Immunological Basis and Implications for Psychoneuroimmunology. Brain, Behavior, and Immunity, 17, S27-S36.

[12]   Fan, S.G., Gao, S., Shao, L., Li, Y.F., Mei, L. and Ding, G.F. (1995) A Factor in Lymph Node and Spleen Induced by Restraint Stress in Mice and Rats Suppresses Lymphocyte Proliferation. Neuroimmunomodulation, 2, 274-281.

[13]   Silberman, D.M., Wald, M. and Genaro, A.M. (2002) Effects of Chronic Mild Stress on Lymphocyte Proliferative Response. Participation of Serum Thyroid Hormones and Corticosterone. International Immunopharmacology, 2, 487-497.

[14]   Neigh, G.N., Bilbo, S.D., Hotchkiss, A.K. and Nelson, R.J. (2004) Exogenous Pyruvate Prevents Stress-Evoked Suppression of Mitogen-Stimulated Proliferation. Brain, Behavior, and Immunity, 18, 425-433.

[15]   Ghanshani, S., Wulff, H., Miller, M.J., Rohm, H., Neben, A., Gutman, G.A., Cahalan, M.D. and Chandy, K.G. (2000) Up-Regulation of the IKCa1 Potassium Channel during T-Cell Activation. Molecular Mechanism and Functional Consequences. Journal of Biological Chemistry, 275, 37137-37149.

[16]   Lewis, R.S. and Cahalan, M.D. (1995) Potassium and Calcium Channels in Lymphocytes. Annual Review of Immunology, 13, 623-653.

[17]   Niiro, H. and Clark, E.A. (2002) Regulation of B-Cell Fate by Antigen-Receptor Signals. Nature Reviews Immunology, 2, 945-956.

[18]   De Coursey, T.E., Chandy, K.G., Gupta, S. and Cahalan, M.D. (1984) Voltage-Gated K+ Channels in Human T Lymphocytes: A Role in Mitogenesis? Nature, 307, 465-468.

[19]   Amigorena, S., Choquet, D., Teillaud, J.L., Korn, H. and Fridman, W.H. (1990) Ion Channel Blockers Inhibit B Cell Activation at a Precise STAGE of the G1 Phase of the Cell Cycle. Possible Involvement of K+ Channels. Journal of Neuroimmunology, 144, 2038-2045.

[20]   Chandy, K.G., De Coursey, T.E., Cahalan, M.D., McLaughlin, C. and Gupta, S. (1984) Voltage-Gated Potassium Channels Are Required for Human T Lymphocyte Activation. Journal of Experimental Medicine, 160, 369-385.

[21]   Partiseti, M., Choquet, D., Diu, A. and Korn, H. (1992) Differential Regulation of Voltage- and Calcium-Activated Potassium Channels in Human B Lymphocytes. Journal of Neuroimmunology, 148, 3361-3368.

[22]   Levite, M., Cahalon, L., Peretz, A., Hershkoviz, R., Sobko, A., Ariel, A., Desai, R., Attali, B. and Lider, O. (2000) Extracellular K+ and Opening of Voltage-Gated Potassium Channels Activate T Cell Integrin Function: Physical and Functional Association between Kv1.3 Channels and Beta1 Integrins. Journal of Experimental Medicine, 191, 1167-1176.

[23]   Beeton, C., Wulff, H., Standifer, N.E., Azam, P., Mullen, K.M., Pennington, M.W., Kolski-Andreaco, A., Wei, E., Grino, A., Counts, D.R., Wang, P.H., LeeHealey, C.J., Andrews, B.S., Sankaranarayanan, A., Homerick, D., Roeck, W.W., Tehranzadeh, J., Stanhope, K.L., Zimin, P., Havel, P.J., Griffey, S., Knaus, H.G., Nepom, G.T., Gutman, G.A., Calabresi, P.A. and Chandy, K.G. (2006) Kv1.3 Channels Are a Therapeutic Target for T Cell-Mediated Autoimmune Diseases. Proceedings of the National Academy of Sciences of the United States of America, 103, 17414-17419.

[24]   Hu, L., Pennington, M., Jiang, Q., Whartenby, K.A. and Calabresi, P.A. (2007) Characterization of the Functional Properties of the Voltage-Gated Potassium Channel Kv1.3 in Human CD4+ T Lymphocytes. Journal of Immunology, 179, 4563-4570.

[25]   Zha, H., Ding, G. and Fan, S. (1992) Serum Factor(s) Induced by Restraint Stress in Mice and Rats Suppresses Lymphocyte Proliferation. Brain, Behavior, and Immunity, 6, 18-31.

[26]   Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent. Journal of Biological Chemistry, 193, 265-275.

[27]   Weir, D.M. (1988) Immunology. Churchill Livingstone, New York.

[28]   Kiecolt-Glaser, J.K., Glaser, R., Gravenstein, S., Malarkey, W.B. and Sheridan, J. (1996) Chronic Stress Alters the Immune Response to Influenza Virus Vaccine in Older Adults. Proceedings of the National Academy of Sciences of the United States of America, 93, 3043-3047.

[29]   Pruett, S.B. (2003) Stress and the Immune System. Pathophysiology, 9, 133-153.

[30]   Satoh, E., Edamatsu, H. and Omata, Y. (2006) Acute Restraint Stress Enhances Calcium Mobilization and Proliferative Response in Splenic Lymphocytes from Mice. Stress, 9, 223-230.

[31]   Li, J., Hu, S., Zhang, C.Q., Yang, H.P. and Ni, C. (2008) Impact of Chronic Restraint Stress on Splenocyte Immunity and Growth of Mouse Forestomach Carcinoma Xenografts in Kunming Mice. Ai Zheng, 27, 471-475.

[32]   Grillot, D.A., Merino, R., Pena, J.C., Fanslow, W.C., Finkelman, F.D., Thompson, C.B. and Nunez, G. (1996) Bcl-X Exhibits Regulated Expression during B Cell Development and Activation and Modulates Lymphocyte Survival in Transgenic Mice. Journal of Experimental Medicine, 183, 381-391.

[33]   Park, C.G., Lee, S.Y., Kandala, G., Lee, S.Y. and Choi, Y. (1996) A Novel Gene Product That Couples TCR Signaling to Fas(CD95) Expression in Activation-Induced Cell Death. Immunity, 4, 583-591.

[34]   Dhabhar, F.S., Malarkey, W.B., Neri, E. and McEwen, B.S. (2012) Stress-Induced Redistribution of Immune Cells— From Barracks to Boulevards to Battlefields: A Tale of Three Hormones—Curt Richter Award Winner. Psychoneuroendocrinology, 37, 1345-1368.

[35]   Wu, W., Sun, M., Zhang, H.P., Chen, T., Wu, R., Liu, C., Yang, G., Geng, X.R., Feng, B.S., Liu, Z.G., Liu, Z.J. and Yang, P.C. (2014) Prolactin Mediates Psychological Stress-Induced Dysfunction of Regulatory T Cells to Facilitate Intestinal Inflammation. Gut, 63, 1883-1892.

[36]   He, Y., Gao, H., Li, X. and Zhao, Y. (2014) Psychological Stress Exerts Effects on Pathogenesis of Hepatitis B via Type-1/Type-2 Cytokines Shift toward Type-2 Cytokine Response. PLoS ONE, 9, e105530.

[37]   Li, H., Zhao, J., Chen, M., Tan, Y., Yang, X., Caudle, Y. and Yin, D. (2014) Toll-Like Receptor 9 Is Required for Chronic Stress-Induced Immune Suppression. Neuroimmunomodulation, 21, 1-7.

[38]   Ishida, Y. and Chused, T.M. (1993) Lack of Voltage Sensitive Potassium Channels and Generation of Membrane Potential by Sodium Potassium ATPase in Murine T lymphocytes. Journal of Immunology, 15, 1610-1620.

[39]   Maltsev, V.A. (1990) Oscillating and Triggering Properties of T Cell Membrane Potential. Immunology Letters, 26, 277-282.

[40]   Hu, D., Wan, L., Chen, M., Caudle, Y., LeSage, G., Li, Q.C. and Yin, D.L. (2014) Essential Role of IL-10/STAT3 in Chronic Stress-Induced Immune Suppression. Brain, Behavior, and Immunity, 36, 118-127.

[41]   Liu, G.H., Dong, Y.L., Wang, Z.X., Cao, J. and Chen, Y.X. (2014) Restraint Stress Alters Immune Parameters and Induces Oxidative Stress in the Mouse Uterus during Embryo Implantation. Stress, 17, 494-503.

[42]   Conforti, L., Petrovic, M., Mohammad, D., Lee, S., Ma, Q., Barone, S. and Filipovich, A.H. (2003) Hypoxia Regulates Expression and Activity of Kv1.3 Channels in T Lymphocytes: A Possible Role in T Cell Proliferation. Journal of Immunology, 170, 695-702.

[43]   Alizadeh, A.A. and Staudt, L.M. (2000) Genomic-Scale Gene Expression Profiling of Normal and Malignant Immune Cells. Current Opinion in Immunology, 12, 219-225.