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Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining

Published online by Cambridge University Press:  09 July 2009

M. Maes ,
J. Lambrechts ,
E. Bosmans ,
J. Jacobs ,
E. Suy ,
C. Vandervorst ,
C. De Jonckheere ,
B. Minner  and
J. Raus
M. Maes*
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
J. Lambrechts
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
E. Bosmans
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
J. Jacobs
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
E. Suy
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
C. Vandervorst
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
C. De Jonckheere
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
B. Minner
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
J. Raus
Affiliation:
Psychiatric Centre, Munsterbilzen; Dr Willems Institute, University of Diepenbeek; Eurogenetics, Tessenderloo, Belgium
*
1 Address for correspondence: Dr M. Maes, Psychiatric Centre, St-Jozef, Abdijstraat, 2, 3751, Munsterbilzen, Belgium.
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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.

Type
Original Articles
Information
Psychological Medicine , Volume 22 , Issue 1 , February 1992 , pp. 45 - 53
Copyright
Copyright © Cambridge University Press 1992

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References

Referemces

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. (1988). Depression and immune function. Stress Medicine 14, 95–103.CrossRefGoogle Scholar
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
Littman, D. R. (1987). The structure of the CD4 and CD8 genes. Annual Review of Immunology 5, 561–584.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
Sanders, M. E., Makgoba, M. W. & Shaw, S. (1988). Human naive and memory T cells. Immunology Today 9, 195–199.CrossRefGoogle ScholarPubMed
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
Swain, S. L. (1983). T cell subsets and the recognition of MHC class. Immunological Review 74, 129–142.CrossRefGoogle ScholarPubMed
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