SYNOPSISSeveral 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.

One of the most consistently reported immunological abnormalities in major depression is blunted ex vivo natural killer cell activity (NKCA). This study was designed to investigate the number and percentage of circulating natural killer cells (NKC) in a group of patients with unipolar depression. In addition, the number and percentage of other phagocytic/cytotoxic cells were determined. The following cell subsets were investigated: number of leukocytes, monocytes, neutrophils, lymphocytes, NKC (CD 16+ or CD56+), and non-MHC-restricted cytotoxic T lymphocytes (CTL) in 17 healthy controls and 79 depressed subjects. There were no differences either in absolute number or percentage of NKC, or CTL between healthy controls, minor, simple major, and melancholic depressed subjects. Depression per se was characterized by a leukocytosis due to monocytosis and neutrophilia. Our results do not support the thesis that depression-related blunted NKCA is caused by a decreased number or percentage of NKC in peripheral blood.

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In this study we describe for the first time the production of stable human B cell lines and clones that secrete IgM antibody specific for human myelin basic protein. The technique based on limiting dilutions of Epstein-Barr virus (EBV)-transformed peripheral B cells from patients with multiple sclerosis precluded the need for preselecting or stimulating antigen-specific B cells. Most of the cell lines were stable for at least 6 months in continuous culture and produced 5-12 micrograms/ml antibody after 2 weeks in culture. The myelin basic protein (MBP)-specific B cells were surface IgM positive, and occurred with a frequency of approximately 1/2500 mononuclear cells in peripheral blood. The successful selection and quantitation of specific B cell clones described here suggests that this technique is well suited for evaluating B cell responses to known and suspected antigens and autoantigens.