Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining | Psychological Medicine | Cambridge Core (original) (raw)

Synopsis

Several studies have reported a suppressed immune function (e.g. blast transformation) during depression. In an attempt to define the cellular basis of the reported immune disorders, the present study investigates the leukocyte cell subset profile of minor, simple major, and melancholic depressives, versus normal controls. We have counted the number of white blood cells (WBC) lymphocytes, monocytes, and granulocytes, while the number of lymphocyte (sub)populations has been identified by phenotype, using monoclonal antibody staining in conjunction with flow cytometry. The following cell surface antigens were determined: CD3+ (pan T), CD19+ (pan B), CD4+ (T helper/inducer), CD8+ (T suppressor/cytotoxic), CD4+CD45RA (T-memory cells), CD4+CD45RA+ (T-virgin cells), surface Ig, class II MHC HLA-DR, and CD25+ (IL-2 receptor). By means of pattern recognition methods, we established distinct immunological changes in minor and simple major depressed and in melancholic patients, setting them apart from the reference population. Depression, per se, is characterized by a higher number of WBC, monocytes, class II MHC HLA-DR, and memory T cells. Minor and simple major depressives exhibited an increased T helper/suppressor ratio. Increased numbers of IL-2 receptor bearing cells are a hallmark for major depression. Melancholics showed an increased number of pan T, pan B and T suppressor/cytotoxic cells. It was concluded that the established immune cell profile of depressed patients may point towards the existence of a systemic immune activation during that illness.

References

American Psychiatric Association (1980). Diagnostic and Statistical Manual of Mental Disorders (3rd edn). APA: Washington, DC.Google Scholar

Arthur, R. P. & Mason, D. W. (1986). T cells that help B-cell responses to soluble antigen are distinguishable from those producing interleukin-2 on mitogenic or allogenic stimulation. Journal of Experimental Medicine 163, 774–786.CrossRefGoogle ScholarPubMed

Besedovsky, H., del-Rey, A., Sorkin, E. & Dinarello, C. A. (1986). Immunoregulatory feedback between interleukin-1 and glucocortinicoid hormones. Science 233, 652–654.CrossRefGoogle ScholarPubMed

Bloemena, E. (1989). Immunosuppressive mechanisms of prednisolone and cyclosporin A. Ph.D. thesis, University of Amsterdam.Google Scholar

Brenner, M. B., McLean, J., Dialynas, D. P., Strominger, J. L., Smith, J. A., Owen, F. L. & Seidman, J. G. (1986). Identification of a putative second T-cell receptor. Nature 322, 145–149.CrossRefGoogle ScholarPubMed

Burton, R. C., Ferguson, P., Gray, M., Hall, J., Hayes, M. & Smart, Y. C. (1983). Effects of age, gender, and cigarette smoking on human immunoregulatory T-cell subsets: establishment of normal ranges and comparison with patients with colorectal cancer and multiple sclerosis. Diagnostic Immunology 1, 216–223.Google ScholarPubMed

Byrne, J. A., Butler, J. L. & Cooper, M. D. (1988). Differential activation requirements for virgin and memory T cells. Journal of Immunology 141, 3249–3257.Google Scholar

Clark, E. A. & Shu, G. (1987). Activation of human B-cell proliferation through surface Bp35 (CD20) polypeptides or immunoglobulin receptors. Journal of Immunology 138, 720–725.CrossRefGoogle ScholarPubMed

Clement, L. T., Yamashita, N. & Martin, A. M. (1988). The functionally distinct subpopulations of human CD4+ helper/inducer T lymphocytes defined by anti-CD45R antibodies derive sequentially from a differentiation pathway that is regulated by activation-dependent post-thymic differentiation. Journal of Immunology 141, 1464–1470.CrossRefGoogle ScholarPubMed

Darko, D. F., Lucas, A. H., Gillin, J. C., Risch, S. C., Golshan, S., Hamburger, R. N., Silverman, M. B. & Janowsky, D. S. (1988). Cellular immunity and the hypothalamic–pituitary axis in major affective disorder: a preliminary study. Psychiatry Research 25, 1–10.CrossRefGoogle ScholarPubMed

Giorgi, J. V. (1986). Lymphocyte subset measurements: significance in clinical medicine. In Manual of Clinical Immunology, 3rd edn (ed. Rose, N. R., Friedman, H. and Fahey, J. L.), pp. 236–246. American Society for Microbiology: Washington.Google Scholar

Giari, J. G., Kincade, P. W. & Mizel, S. B. (1984). Interleukin-1 mediated induction of kappa-light chain synthesis and surface immunoglobulin expression on pre-B cells. Journal of Immunology 132, 223–228.CrossRefGoogle Scholar

Hamilton, M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 56–61.Google Scholar

Hoffman, M. K. (1988). The requirement for high intracellular cyclic adenosine monophosphatase concentrations distinguishes two pathways of B cell activation induced with lymphokines and antibody to immunoglobulin. Journal of Immunology 140, 580–582.CrossRefGoogle Scholar

Imboden, J. & Stobo, J. D. (1985). Transmembrane signalling by the T-cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. Journal of Experimental Medicine 161, 446–456.CrossRefGoogle ScholarPubMed

Irwin, M. & Gillin, J. C. (1987). Impaired natural killer cell activity among depression patients. Psychiatry Research 20, 181–182.CrossRefGoogle Scholar

Irwin, M., Patterson, T., Smith, T. L., Caldwell, C., Brown, S. A., Gillin, J. C. & Grant, I. (1990). Reduction of immune function in life stress and depression. Biological Psychiatry 27, 22–30.CrossRefGoogle ScholarPubMed

Kishimoto, T. & Ishizaka, K. (1975). Regulation of antibody response in vitro. IX. Induction of secondary anti-hapten IgG antibody response by anti-immunoglobulin and enhancing soluble factor. Journal of Immunology 144, 585–591.CrossRefGoogle Scholar

Ko, H. S., Fu, S. M., Winchester, R. J., Yu, T. Y. & Kunkel, H. G. (1979). Ia determinants on stimulated human T lymphocytes: occurrence on mitogen- and antigen-activated cells. Journal of Experimental Medicine 150, 246–257.CrossRefGoogle Scholar

Kowalski, B. R. (1977). Chemometrics: Theory and Application. American Chemical Society: Washington.CrossRefGoogle Scholar

Kronfol, Z., Silva, J., Greden, J., Dembinsky, S., Gardner, R. & Carroll, B. (1983). Impaired lymphocyte function in depressive illness. Life Sciences 33, 241–247.CrossRefGoogle ScholarPubMed

Kronfol, Z., House, D. J., Silva, J. Jr., Greden, J. & Carroll, B. J. (1986). Depression, urinary free cortisol excretion and lymphocyte function. British Journal of Psychiatry 148, 70–73.Google Scholar

Lew, W., Oppenheim, J. J. & Matsushima, K. (1988). Analysis of the suppression of IL-1-alpha and IL-1-beta production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. Journal of Immunology 140, 1895–1902.CrossRefGoogle ScholarPubMed

Lowenthal, J. W., Zubler, R. H., Nabholz, M. & MacDonald, H. R. (1985). Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature 315, 669–672.Google Scholar

MacKeen, L., Brown, M., Kung, P. C., Yasuda, N., Harrington, D., Hinuma, Y., Weisenburger, D., Lai, P. & Purtilo, D. (1986). Serum interleukin-2 receptor as a marker for active T cell malignancies. Federation Proceedings 45, 454.Google Scholar

Maes, M., Bosmans, E., Suy, E., Minner, B. & Raus, J. (1989 a). Impaired lymphocyte stimulation by mitogens in severely depressed patients. A complex interface with HPA-axis hyperfunction, noradrenergic activity and the ageing process. British Journal of Psychiatry 155, 793–798.CrossRefGoogle ScholarPubMed

Maes, M., Bosmans, E., Suy, E., Minner, B. & Raus, J. (1989 b). Immune cell parameters in severely depressed patients: negative findings. Journal of Affective Disorders 17, 121–128.CrossRefGoogle ScholarPubMed

Maes, M., Cosyns, P., Maes, L., D'Hondt, P. & Schotte, C. (1990 a). Clinical subtypes of unipolar depression. Part I. A validation of the vital and non-vital clusters. Psychiatry Research 34, 29–41.CrossRefGoogle Scholar

Maes, M., Schotte, C., Maes, L. & Cosyns, P. (1990 b). Clinical subtypes of unipolar depression. Part II. Quantitative and qualitative clinical differences between the vital and non-vital depression groups. Psychiatry Research 34, 43–57.Google Scholar

Maes, M., Maes, L., Schotte, C., Vandewoude, M., Martin, M., D'Hondt, P., Blockx, P., Scharpé, S. & Cosyns, P. (1990 c). Clinical subtypes of unipolar depression. Part III. Quantitative differences in various biological markers between the cluster analysis-generated non-vital and vital depression classes. Psychiatry Research 34, 59–75.CrossRefGoogle Scholar

Maes, M., Vandewoude, M., Schotte, C., Maes, L., Martin, M. & Blockx, P. (1990 d). A revised interpretation of the post-dexamethasone ACTH and cortisol values in unipolar depressed females. Psychiatry Research 34, 147–160.CrossRefGoogle Scholar

Maes, M., Bosmans, E., Suy, E., Minner, B. & Raus, J. (1991 a). A further exploration of the relationships between immune parameters and the HPA-axis activity in depressed patients. Psychological Medicine 21, 313–320.CrossRefGoogle ScholarPubMed

Maes, M., Bosmans, E., Suy, E., Vandervorst, C., De Jonckheere, C. & Raus, J. (1991 b). Antiphospholipid, anti-nuclear, Epstein–Barr and cytomegalovirus antibodies, and soluble interleukin-2 receptors in depressive patients. Journal of Affective Disorders (in the press).Google Scholar

Maes, M., Bosmans, E., Suy, E., Vandervorst, C., De Jonckheere, C., Minner, B. & Raus, J. (1991 c). Depression-related disturbances in mitogen-induced lymphocyte responses, inlerleukin-1β, and soluble interleukin-2-receptor production. Acta Psychiatrica Scandinavia (in the press).Google Scholar

Maino, V. C., Hayman, M. J. & Crumpton, M. J. (1975). Relationship between enhanced turnover of phosphatidylinositol and lymphocyte activation by mitogen. Biochemical Journal 146, 247–252.CrossRefGoogle Scholar

Massart, L. & Kaufman, L. (1983). In The Interpretation of Analytical Chemical Data by the Use of Cluster Analysis (ed. Elving, P. J. and Winefordner, J. D.), pp. 101–138. John Wiley and Sons: New York.Google Scholar

Massart, D. L., Vandeginste, B. G. M., Deming, S. N., Michotte, Y. & Kaufman, L. (1988). Chemometrics: a Textbook. Elsevier: Amsterdam.Google Scholar

Mercep, M., Bonifacino, J. S., Garcia-Morales, P. et al. (1988). T cell CD3-heterodimer expression and coupling to phosphoinositide. Science 242, 571–573.CrossRefGoogle Scholar

Meuer, S. C., Acuto, O. & Hussey, R. E. (1983). Evidence for the T3-associated OOK heterodimer as the T-cell antigen receptor. Nature 303, 808–810.CrossRefGoogle Scholar

Miyawaki, T., Taga, K., Nagaoki, T., Seki, H., Suzuki, Y. & Taniguchi, N. (1984). Circadian changes of T lymphocyte subsets in human peripheral blood. Clinical and Experimental Immunology 55, 618–622.Google ScholarPubMed

Möller, G. (1975). One non-specific signal triggers B lymphocytes. Transplant Review 23, 126–137.Google ScholarPubMed

Nadler, L. M., Anderson, K. C., Marti, G., Bates, M., Park, E., Daley, J. F. & Schlossman, S. F. (1983). B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes. Journal of Immunology 131, 244–250.CrossRefGoogle Scholar

Nieto, M. A. & Lopez-Rivas, A. (1989). II-2 protects T lymphocytes from glucocorticoid-induced DNA fragmentation, and cell death. Journal of Immunology 142, 4166–4170.CrossRefGoogle Scholar

Oppenheim, J. J., Kovacs, E. J., Matsushima, K. & Durum, S. K. (1986). There is more than one interleukin I. Immunology Today 7, 45–56.Google Scholar

Reed, J. C., Abidi, A. S., Alpers, J. D., Hoover, R. G., Robb, R. J. & Nowell, P. C. (1986). Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression. Journal of Immunology 137, 150–154.Google Scholar

Rivas, A., Takada, S. & Koide, J. (1988). CD4 molecules are associated with the antigen receptor complex on activated but not resting T cells. Journal of Immunology 140, 2912–2928.CrossRefGoogle Scholar

Robb, R. J. (1985). Interleukin 2 and its cell-surface receptor. Behring Institut Mitteilungen 77, 56–67.Google Scholar

Rosenwasser, L. J. (1986). Monocyte and macrophage function. In Manual of Clinical Laboratory Immunology (ed. Rose, N. R., Friedman, H. and Fahey, J. L.), pp. 321–325. American Society for Microbiology: Washington.Google Scholar

Schleifer, S. J., Keller, S. E., Meyerson, A. T., Raskin, M. J., Davis, K. L. & Stein, M. (1984). Lymphocyte function in major depressive disorder. Archives of General Psychiatry 41, 484–486.Google Scholar

Smith, K. A. (1986). Interleukin-2: inception, impact, and implications. Science 240, 1169–1176.CrossRefGoogle Scholar

Spickett, G. P., Brandon, M. R., Mason, D. W., Williams, A. F. & Woollett, G. R. (1983). MRC OX-22, a monoclonal antibody that labels a new subset of T lymphocytes and reacts with the high molecular weight form of the leukocyte-common antigen. Journal of Experimental Medicine 158, 795–810.Google Scholar

Spitzer, R. L., Williams, J. B. W. & Gibbon, M. (1985). Structured Clinical Interview for DSM-III, Patient Version. New York State Psychiatric Institute: New York.Google Scholar

Springer, T. A., Dustin, M. L., Kishimoti, T. K. & Marlin, S. D. (1987). The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annual Review of Immunology 5, 223–252.CrossRefGoogle ScholarPubMed

Stites, D. P. (1987). Clinical laboratory methods for detection of cellular immune function. In Basic and Clinical Immunology, 6th edn (ed. Stites, D. P., Stobo, J. D. and Wells, J. V.), pp. 285–303. Prentice-Hall International: London.Google Scholar

Stone, B. A., Koopersmith, T. B., Quinn, K., Quinn, P. & Marrs, R. P. (1989). Levels of interleukin-2 receptor in serum of patients during the menstrual cycle and following embryo/gamete transfer. American Journal of Reproductive Immunology 20, 114–116.Google Scholar

Waldmann, T. A. (1986). The structure, function, and expression of interleukin 2 receptors on normal and malignant lymphocytes. Science 232, 727–732.CrossRefGoogle ScholarPubMed

Warner, N. L., Byrt, P. & Adam, G. L. (1970). Blocking of the lymphocyte antigen receptor site with anti-immunoglobulin sera in vitro. Nature 226, 942–943.Google Scholar

Warner, N. L. & Fahey, J. L. (1986). Introduction. In Manual of Clinical Laboratory Immunology, 3rd edn (ed. Rose, N. R., Friedman, H. and Fahey, J. L.). American Society for Microbiology: Washington.Google Scholar

Wassmer, P., Chan, C., Logdberg, L. & Shevach, E. M. (1985). Role of the L3T4-antigen in T cell activation. II. Inhibition of T cell activation by monoclonal anti-L3T4 antibodies in the absence of accessory cells. Journal of Immunology 135, 2237–2242.Google Scholar

Whitcomb, R. W., Linehan, W. M., Wahl, L. M. & Knazek, R. A. (1988). Monocytes stimulate cortisol production by cultured human adrenocortical cells. Journal of Clinical Endocrinology and Metabolism 66, 33–38.CrossRefGoogle ScholarPubMed

Williams, J. B. W. & Spitzer, R. K. (1982). Research diagnostic criteria and DSM-III: an annotated comparison. Archives of General Psychiatry 39, 1283–1289.CrossRefGoogle ScholarPubMed

Winchester, R. J. & Ross, G. D. (1986). Methods for enumerating cell populations by surface markers with conventional microscopy. In Manual of Clinical Laboratory Immunology, 3rd edn (ed. Rose, N. R., Friedman, H. and Fahey, J. L.), pp. 212–225. American Society for Microbiology: Washington.Google Scholar