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A 22-year-old man who underwent syngeneic bone marrow transplantation (BMT) for acute lymphoblastic leukemia acquired a human immunodeficiency virus (HIV) infection by transfusion of blood products from a donor at risk. The manifestations were acute encephalopathy together with immune thrombocytopenia in the early posttransplant period, and acquired immunodeficiency syndrome (AIDS) developed 20 months after BMT. Because he had a syngeneic donor, the possibility of reconstituting the immune system was investigated by repeated transfer of healthy syngeneic lymphocytes and by combining repeated transfer of syngeneic lymphocytes with the antiviral agent suramin to protect the infused leukocytes from being attacked by HIV. No improvement was observed clinically or in the patient's immune functions by these efforts.

To evaluate the clinical significance of the liver cell membrane autoantibody (LMA) assay, we studied the presence, titre and immunoglobulin classes of LMA in 162 patients with various liver diseases and 156 controls. LMA was detected predominantly in patients with HBsAg-negative chronic active hepatitis (73% of 26 patients), but was also found in lower prevalences in other liver diseases, such as primary biliary cirrhosis syndrome (43% of 28 patients). LMA-positive primary biliary cirrhosis patients could be distinguished from LMA-positive patients with other liver diseases by the virtual absence of IgG class LMA. The LMA assay adds to the panel of assays for non-organ-specific autoantibodies in that it is more specific for autoimmune liver disease and in that it increases the diagnostic yield of autoantibody assays, e.g. in HBsAg-negative chronic active hepatitis from 77 to 92%. Immunosuppressive therapy status and biochemical parameters of disease activity, such as transaminase values, did not show a statistically significant relationship with the prevalence, the titre and the immunoglobulin class of LMA. It is concluded, that LMA is a sensitive and specific diagnostic marker for autoimmune liver disease.

The presence of proteins (p17 and p24 core proteins, gp41 envelope protein) and mRNA (gag/pol and env gene segments) of human immunodeficiency virus type-1 (HIV-1) was analyzed on frozen tissue sections of lymph nodes from HIV-1 infected individuals. Thirty-one lymph nodes were categorized in the stages of follicle hyperplasia (n = 18), follicle degeneration (n = 5), and total depletion (n = 8). The follicle dendritic cells in germinal centers showed the presence of core proteins and, to a lesser extent, gp41. The staining patterns, being similar to those of immunoglobulins, suggested that they occur in the form of immune complexes. In addition there were solitary cells expressing viral protein, in particular gp41, and mRNA. The number of mRNA-positive cells was very low: about five positive cells were observed in a tissue section with about ten (hyperplastic) follicles. HIV-1-mRNA-positive cells were observed both in follicles and interfollicular areas and showed no differences between various stages. The extent and intensity of distinct HIV-1 proteins and HIV-1-mRNA gene segments in follicles were significantly correlated, as was their presence in interfollicular areas. No significant correlation was found between the presence of HIV-1 components in follicles and in interfollicular areas. This indicates that processes involving HIV-1 components occur in a segregated manner in both lymph node compartments. The presence of HIV-1 components did not correspond to any clinical classification (CDC criteria), nor to other histochemical characteristics. An exception was the correlation between gp41-positive cells and CD1-positive interdigitating cells in the interfollicular areas.

Two sisters aged 13 and 19 years suffering from familial Cushing's syndrome due to nodular adrenocortical dysplasia are described. Pituitary adrenocortical function tests indicated the presence of adrenal autonomy. Adrenal scintigraphy showed bilateral symmetrical uptake indicating the bilateral character of the autonomous process. Complete adrenalectomy was performed in both girls. The adrenals were of about normal weight showing numerous dark brown pigmented nodules and small perivascular lymphocytic infiltrates. Serum immunoglobulin preparations obtained from both girls stimulated adrenocortical cell growth in a cytochemical bioassay system. It is proposed that circulating growth factors may be involved in the pathogenesis of the disease.

We previously observed that nude rats after implantation of cultured thymic fragments (CTF) of allogeneic origin manifest in vitro alloreactivity to the donor haplotype, but not to host haplotype. We here extend preliminary data that this in vitro alloreactivity is not accompanied by in vivo rejection of skin transplant from donor CTF origin. This discrepancy between in vivo and in vitro alloreactivity may suggest the presence of peripheral in vivo suppressive mechanisms, which are not active in in vitro assay systems. After implantation of CTF from two different allogeneic strains, however, skin transplants of either one of the donor strains are rejected. We conclude that education of both types of alloreactivity has occurred in the respective CTF's. This latter observation indicates that the suppressive mechanisms hypothesized above, if existent at all, obviously are not sufficiently potent to suppress the alloreactivity which has been generated in a CTF which expresses MHC antigens irrelevant to the alloreaction inducing determinants. If the tolerance to donor CTF is not due to a peripheral tolerance/suppression, it might bear relation to events occurring during precursor T-cell processing in the grafted CTF. The state of chimaerism in the graft reported earlier may explain this tolerance.

Four cases of malignant B-cell lymphoma characterized by a conspicuous component of tumour cells with markedly lobatated nuclei are described. Two exhibited a follicular and two a diffuse growth pattern. The tumour cell population formed a continuous spectrum comprising both cells resembling normal follicle centre cells and multilobated lymphoma cells. Cytomorphological analysis of the multilobated cell group indicated a differentiation series from centroblast-like cells with moderately lobated nuclei to large and medium-sized cells with marked nuclear lobation which revealed features of centrocytes. In three cases (1, 3, and 4) the majority of these multilobated cells showed plasmacytoid differentiation in their cytoplasm in conjunction with the synthesis of monotypical cytoplasmic immunoglobulin. No plasmacytoid features were present in a fourth case (2). In only one case (4) monotypical surface immunoglobulin was detectable on the tumour cells. A close relationship between the multilobated tumour cells and follicle centre cells was further substantiated by the finding of a similar cell variant in the follicle centres of a control group of non-neoplastic lymph nodes. It included cells with plasmacytoid differentiation which synthesized polytypical immunoglobulin. We consider this type of B-cell lymphoma with a conspicuous component of cells with lobated nuclei as a variant of malignant lymphoma, centroblastic/centrocytic.

To evaluate the role of some immunological phenomena involved in the pathogenesis of preeclamptic toxaemia, we studied the humoral immune reactivity in patients with preeclamptic toxaemia during the third trimester of pregnancy, and three days and six weeks after delivery. The results were compared with those of patients with intrauterine growth retardation and with uneventful pregnancy. During the third trimester, patients with complicated preeclamptic toxaemia had significantly lower IgG, CH50, C4 and C3 levels than normal pregnants. Post-partum levels of IgM were significantly higher than in all other groups of patients. Circulating immune complexes were not detectable by a C1q binding assay in patients and controls. However, with a conglutinin binding assay and a granulocyte phagocytosis test complexes were demonstrable in patients with complicated preeclampsia (incidence 44% and 33%, respectively). In addition, 66% of these patients showed deposits of immunoglobulins and complement components in superficial blood vessels of the skin biopsy, suggestive of the presence of tissue deposits of immune complexes. This was found in about 30% of the other patient groups and in none of control pregnants. Allo-antibodies to lymphocytes were present in 63% of complicated preeclamptic toxaemia patients and 22% of normal pregnants. Our data show several changes in humoral immune reactivity in preeclamptic toxaemia which may contribute to the pathogenesis of this disorder.

Cultured thymic fragments correspond to the thymic microenvironment depleted of lymphocytes and dendritic cells. When these fragments are implanted under the kidney capsule of congenitally athymic rats, lymphocytes and dendritic cells of host origin enter the graft and induce thymus-dependent immunity in the recipient. This paper describes the ultrastructure of the fragments and the changes that occur during the restoration of normal thymic architecture. At the end of the culture period of 6-9 days and in the early stages after implantation, the grafts consist of keratin-containing epithelial cells of unusual morphology that can be labelled with antibodies raised against the epithelium of the mid/deep cortex and the subcapsule/medulla. Normal thymic architecture develops, including nerves and blood vessels, as lymphocytes populate the environment, and by 4-6 weeks the epithelial cells are the same phenotypically and ultrastructurally as those found in normal rat thymus. However, some areas without lymphocytes still contain the atypical epithelial cells seen before implantation. Large multinucleated giant cells are also present with a few associated epithelial cells of subcapsular/medullary phenotype. In conclusion, the cultured thymic fragments contain a hitherto unknown precursor epithelial cell with an atypical ultrastructure and phenotype that is not seen in normal development.

In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/ml) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 microgram IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA deficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA antibodies and the appearance of anaphylactic reactions after transfusion of IgA.

We investigated the in vitro effect of cultured human thymic epithelial monolayer cells on mononuclear cells (MNC) from patients with Acquired Immune Deficiency Syndrome (AIDS) and AIDS-related complex (ARC). Patients having undergone bone-marrow transplantation (BMT), who showed a similar deficiency of T-lymphocytes expressing CD4 (Leu-3, T4), and healthy blood donors served as controls. Most epithelial monolayer cells were of thymic medulla origin, as documented using a panel of monoclonal antibodies to thymic epithelial cells. In AIDS/ARC patients the CD4-positive cells (ranging between 4 and 30% of MNC) increased by a factor of 1.56 (s.e.m. 0.15, n = 12) during a 2 h incubation on the monolayer. Human fetal lung fibroblasts were inactive in this respect. There was no consistent change in cells expressing CD3 (Leu-4, T3), CD5 (Leu-1) or CD8 (Leu-2, T8). In BMT patients and healthy controls, neither thymus epithelium nor fibroblasts had any effect on T cell marker expression. Incorporation of tritiated thymidine by stimulated or unstimulated lymphocytes was increased after incubation for 3 days on either epithelium or fibroblasts. We conclude that CD4 expression is induced on MNC from AIDS/ARC patients during a 2 h incubation on epithelial monolayers.

The diagnostic relevance of different tests for detection of surface immunoglobulin on tumour cells of B-type non-Hodgkin's lymphomas (B-NHL) was investigated by comparison of the direct antiglobulin rosetting reaction (DARR) in suspension with two-colour direct immunofluorescence (DIF) on frozen tissue sections. In benign lymph nodes (n = 27) the kappa/lambda ratio by DARR test ranged from 0.9 to 2.8. Tested by suspension and frozen tissue analysis, light chain restriction was found in 24 and 27 of 31 cases of B-NHL, respectively. Heavy chain restriction was found in half of the cases (14 of 26) studied in suspension and in almost all (28 of 31) tested on sections. In 9 cases DARR tests showed restriction of more than one Ig class on tumour cells, which was infrequent (2 of 28) in frozen section analysis. Although both tests appeared valuable for routine diagnostic purposes, we found the DIF analysis on tissue sections somewhat more discriminative, especially in detection of heavy chain restriction in B-NHL.

The immunohistological findings in the thymus after bone marrow transplantation were studied in autopsy samples from 12 patients who had received allogeneic grafts as treatment for acute leukemia. The findings were compared with those in samples from normal individuals and from conventionally treated leukemic patients. The thymuses were hyperinvoluted in all grafted and nongrafted subjects. The remnants were composed of subcapsular and medullary epithelium which expressed the same phenotype as the normal thymus controls. Most samples also contained small remnants of cortical epithelium which lacked normal expression of HLA-DR antigens. The intraepithelial and stromal thymic lymphocytes were virtually all mature T cells, and no immature cortical thymocytes were seen. With the use of HLA-typing methods in 2 recipients of one-haplotype-matched grafts no donor cells could be identified in any of the thymic components. These findings provide no evidence for a functional role for the thymus in the differentiation of donor-derived precursor T cells, at least in the early period after transplantation.