B. S. Rabin

Experimental studies in rats showed that immunization of the pregnant female led to the transplacental immunization of her fetuses. The possibility that this also occurred in humans was explored by immunizing 42 pregnant women with tetanus toxoid (2.5 or 5 Lf) in the fifth and eighth months of pregnancy and comparing the immune responses of their offspring with the responses of the offspring of 25 unimmunized mothers. Only the offspring of the immunized mothers were sensitized to tetanus. IgM antitetanus antibodies were in their blood before immunization with diphtheria, pertussis, tetanus vaccine (DPT), they had a more rapid (P less than 0.01) response to DPT immunization, and they were still highly sensitized (P less than 0.01) to tetanus 13 mo after birth. In addition, pregnancy had no immunosuppressive effect (P less than 0.05) on the responses of the mothers to tetanus toxoid. Thus, transplacental immunization occurs in humans; it enhances the response of the offspring to subsequent immunization, and it could be used to circumvent the necessity for immunization in early neonatal life.

A number of assays were performed to assess immunologic function in 28 patients with clinically well-defined schizophrenia. Our data provide laboratory evidence that patients with schizophrenia have characteristics consistent with an autoimmune process, directed to components of the brain, which may participate in either the pathogenesis or etiology of schizophrenia. One-third of our patients had a clinically evident autoimmune syndrome unrelated to their psychiatric illness. Of the nine patients with an autoimmune disease, two had one autoantibody in their serum and five had more than one autoantibodies. Twelve of eighteen patients without clinical evidence of autoimmune disease had no detectable autoantibodies. Mitogenic responses to PHA and PWM were significantly reduced in the patient population when compared to controls. Fifty percent of the patients had an increased percentage (greater than 5%) of blood-borne HLA-DR (+) OKT4 (+) T-helper lymphocytes. Immune reactivity toward brain antigens was sought by measuring lymphocyte transformation to a saline extract of frontal lobe, and by immunoblotting of antigens extracted from frontal lobe, cingulate gyrus, interventricular septum, and hippocampus. Lymphocyte transformation did not reveal differences between patient and control groups. Normal sera were found to contain antibody to some of these brain antigens. However, patients with schizophrenia had antibody to antigens of the hippocampus, septal region and cingulate gyrus which were not encountered during analysis of normal sera.

To determine whether the lymphocytes recovered by bronchoalveolar lavage (BAL) are representative of the cells found in lung tissue, we identified and enumerated lymphocyte phenotypes directly in lung tissue and lavage fluid with monoclonal antibodies (Leu 4-total T, Leu 3-helper T, Leu 2-suppressor/cytotoxic T cells) and an avidin-biotin peroxidase method in 6 patients with sarcoidosis and 6 patients with idiopathic pulmonary fibrosis (IPF). We found that the absolute numbers of each phenotype and the ratios of Leu 3/Leu 4, Leu 2/Leu 4, and Leu 3/Leu 2 in lavage fluid and tissue correlated well for both groups of patients. This supports the notion that the lymphocytes recovered by BAL are representative of the cells present in the lung. However, when cell recovery was expressed as the number per milliliter of recovered lavage fluid, there were no significant correlations between lavage fluid and tissue for any phenotype in the IPF group. The degree of restrictive impairment was significantly greater and the lavage fluid recovery was significantly lower in this group than in the sarcoid group. Thus, the lymphocytes recovered by BAL appear to mirror the types of cells found in lung tissue in these 2 forms of diffuse interstitial disease, but this relationship may not hold when there is a severe restrictive impairment and a low recovery of lavage fluid.

Mononuclear cells in the areas of "piecemeal" necrosis in hepatic tissues from patients with different liver diseases were subtyped using monoclonal antibodies and the avidin-biotin-peroxidase complex method. T lymphocytes were the predominant infiltrating cell type in this lesion (greater than 75% of mononuclear cells) regardless of the etiology of the liver disease. M1-positive cells represented about 20% of the infiltrate. B cells were absent and rare Leu-7-positive cells (killer, natural killer) showed random tissue distribution in both the periportal areas and the parenchyma. In contrast, the T8+ (suppressor-cytotoxic) lymphocytes accumulated selectively in the areas of piecemeal necrosis, where the tissue T4/T8 ratios were consistently less than 1. T8+ lymphocytes were also more numerous than T4+ cells around the hepatitis B surface antigen-positive hepatocytes in piecemeal necrotic areas of livers from patients with hepatitis B surface antigen-positive chronic active hepatitis. In liver tissues of patients with primary biliary cirrhosis, alcoholic cirrhosis, chronic active hepatitis, and rejecting liver allografts, selective accumulations of T8+ lymphocytes at the sites of hepatocyte necrosis were a characteristic and uniform finding. This subpopulation of lymphocytes may be an important part of the immunologically mediated destruction of hepatocytes that occurs in chronic active liver diseases and is characterized by piecemeal necrosis.

Previous studies have demonstrated that stressors alter cellular immune system function, and increase the activity of locus coeruleus neurons. Furthermore, stressors increase the release of corticotropin-releasing hormone (CRH) and locus coeruleus neurons are activated by CRH. Thus, the present study examined whether activation of the locus coeruleus by infusion of CRH modulates the function of blood and spleen lymphocytes assessed in vitro. CRH (100 ng) was administered into the region of the locus coeruleus in awake rats 1 hr before spleen and peripheral blood lymphocytes were collected for culture with nonspecific mitogens. Unilateral or bilateral microinfusion of CRH into the locus coeruleus produced a decrease in blood and spleen T-lymphocyte mitogenic responses to phytohemagglutinin, ConA, and an antibody to the T-lymphocyte antigen receptor. In contrast, infusion of saline into the locus coeruleus or CRH into the surrounding region of the dorsal pons did not alter spleen or blood lymphocyte responses. Plasma concentrations of adrenocorticotropic hormone, corticosterone, and IL-6 were increased by CRH infusion into the locus coeruleus. These results suggest that CRH-evoked activation of the locus coeruleus stimulates the hypophysial adrenal axis, possibly activates the sympathetic nervous system, and results in immunosuppression. Comparable changes in lymphocyte and hormone responses are produced by an aversive stimulus or a conditioned stressor, suggesting that activation of the locus coeruleus may be a component of stressor-induced immune alterations.