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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.

In an attempt to delineate the pathophysiology underpinning the previously reported blunted lymphocyte responses to mitogenic stimulation in depressed patients, we measured the following immune variables in 28 depressives and 10 healthy controls: pre- and postdexamethasone (1 mg orally) lymphocyte responses to various mitogens, such as phytohaemagglutinin (PHA), and the PHA-induced accumulation of interleukin-1 beta (Il-1 beta) and soluble interleukin-2-receptors (sIl-2Rs) in culture supernatants. In the predexamethasone state, we found significantly more mitogen-stimulated blastogenesis in minor depressives vs healthy controls and major depressives. In depressed subjects there was a significant inverse relationship between the severity of illness and the mitogen-induced lymphocyte responses. Melancholics exhibited significantly more Il-1 beta accumulation in PHA culture supernatant than healthy controls. In healthy controls--but not in depressed patients--the sIl-2R accumulation perfectly reflects the magnitude of the PHA-induced lymphocyte stimulation. Dexamethasone administration significantly suppressed the lectin-induced blastogenesis and the Il-1 beta production rate in normal volunteers, whereas depressives exhibited dexamethasone nonsuppression in those factors. Healthy controls exhibited significantly less postdexamethasone blast transformation, Il-1 beta and sIl-2Rs accumulation in culture supernatant than the depressed patients.

We determined the following immune parameters in drug-free, major depressed patients and in age- and sex-matched healthy controls: the number and percentage of interleukin-2 receptor (IL-2R) bearing cells (CD25⁺, anti-TAC), serum circulating levels of soluble (s)IL-2Rs, the pre- and postdexamethasone phytohemagglutinin (PHA)-induced accumulation of sIL-2Rs in culture supernatant, and the number of T helper (CD4⁺) and T suppressor (CD8⁺) cells. In comparison with normal volunteers, patients with major depression had a higher number and percentage of CD25⁺ cells, higher concentrations of serum circulating sIL-2Rs, higher supernatant sIL-2Rs after stimulation with PHA, and a higher number of CD4⁺ cells. The CD4⁺/CD8⁺ ratio and the number of CD4⁺ cells were significantly and positively related to the number of cells expressing the CD25⁺ antigen. These results may indicate that depressed patients display an increased number of T cells in an early phase of activation.

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