Increased intensities of fas expression on peripheral T-cell subsets in severe autoimmune thyroid disease.

Fas (CD95)-Fas ligand (FasL; CD178)-induced apoptosis is necessary for the maintenance of self-tolerance. To clarify whether or not any abnormalities in the Fas-FasL system exist in patients with autoimmune thyroid disease (AITD), we examined the expression of Fas and FasL on peripheral T lymphocytes by three-color flow cytometry in 113 patients with AITD and 49 healthy controls. The intensities of Fas expression in both CD4(+) and CD8(+) T cells decreased in thyrotoxic patients with Graves' disease (GD), but increased in both patients with severe Hashimoto's disease (HD) undergoing treatment and seriously intractable patients with GD continuously positive for thyrotropin (TSH) receptor antibody despite treatment with antithyroid drugs for more than 5 years. The proportion of Fas expression was increased in CD4(+) T cells from patients with untreated GD, and in CD8(+) T cells from patients with severe HD. The proportion of CD8(+) T cells decreased in patients with severe HD. FasL were not expressed on T cells in controls and patients with AITD. These results indicate that (1). the intensities of Fas expression on peripheral T cells increase in severe autoimmune thyroid diseases and (2). both the intensity and the proportion of Fas expression may be important for the induction of apoptosis.     

T-cell receptor genes in autoimmune mice: T-cell subsets have unexpected T-cell receptor gene programs.

Two unique cell subsets have been identified in the autoimmune-prone MRL/MP lpr/lpr and C3H/HeJ gld/gld murine strains that have the Lyt-2-,L3T4-,Thy-1+, and Lyt-2-,L3T4-,Ia-,Thy-1- phenotypes, respectively. We have now found that these cells express T-cell receptor proteins on their surface. Our observations further indicate that the expression of the Thy-1 antigen does not correlate with the expression of alpha-chain and beta-chain T-cell receptor polypeptides. Interestingly, T-cell receptor gamma-chain RNA expression may be influenced or correlate with Thy-1 molecular expression. These studies indicate unusual relationships of different cell-surface structures that may reflect unexpected developmental programs.     

Relation of CD30 molecules on T-cell subsets to the severity of autoimmune thyroid disease.

The prognosis of patients with autoimmune thyroid disease (AITD) varies. To clarify the immunologic differences among patients with various severities of AITD, we examined two types of molecules on peripheral T lymphocytes: CD195 (CCR5), which express dominantly on CD4(+) type 1 helper T (T(H)1) cells, and CD30, which is known as a marker of CD4(+) type 2 helper T (T(H)2) cells and a regulatory molecule of CD8(+) autoreactive cytotoxic T cells. We found presence of patients with high proportion (> 9%) of CD30 expression in CD4(+) cells in a group of patients with Graves' disease (GD) in remission compared to the patients with intractable GD and a decrease in the intensity of CD30 expression on CD8(+) cells from patients with severe Hashimoto's disease (HD) treated for hypothyroidism compared to patients with untreated and euthyroid HD. There was no difference in CD195 expression between these patients with GD or HD with different severities, but there was a decreased intensity of CD195(+) cells in thyrotoxic patients with GD. These results indicate that CD30 molecules on CD4(+) and CD8(+) cells may be related to the severities of GD and HD, respectively.     

Cardiac involvement in systemic autoimmune disease

Systemic autoimmune diseases form a diverse group which includes: systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, dermato-polymyositis, Wegener's granulomatosis, Sj?gren syndrome. Although multisystem involvement is the hallmark of these diseases, the heart seems to be less affected than other organ systems. The aim of the study was to study possible cardiac abnormalities in patients with documented systemic autoimmune diseases and to assess whether there was any relation between antiphospholipid, anti-dsDNA antibodies and myocardial dysfunction findings. 76 patients (53 with SLE, 9 with MCTD, 8 with scleroderma, 6 with Wegener's granulomatosis) were subjected to our study, 69% of these patients manifested cardiac involvement, based on two-dimentional echocardiografic examination (36%--post-inflammatory valvular thickening, 20%--pericardial effusions, 15%--valvular regurgitation, 7%--left atrial enlargement, 5%--left ventricular hypertrophy, 4%--left ventricular dysfunction). None of the patients showed characteristic, acute Libman-Sacks endocarditis, which probably can be explained by chronic corticosteroid-treatment. Clinical evidence of cardiac abnormalities has been observed, in as many as 58% of cases with positive echocardiographic findings. The frequency and extend of cardiac pathology positively correlated with the detection of antiphospholipid antibodies. No such relationship was observed in patients with the presence of very high titers of antinuclear antibodies (anti-dsDNA). In conclusion, our results indicate that echocardiography is a useful method for assessment and monitoring cardiac involvement in the systemic autoimmune diseases.     

Pulmonary manifestations of systemic autoimmune disease

Patients with systemic autoimmune disease may present with a number of different pulmonary manifestations. In order to recognise, diagnose and manage these manifestations, it is necessary to have a working knowledge of the anatomy and physiology of the thorax. This chapter will describe the clinical symptoms and clinical examination findings in patients who may have underlying pulmonary disease. It will describe the investigations that can be used to confirm or refute a possible diagnosis and describe approaches to managing these complex clinical cases. The importance of multidisciplinary team working using the skills of clinicians, radiologists and pathologists will be highlighted. The use of high-resolution computed tomography scanning of the thorax to help to delineate the type of interstitial lung disease will be described and some of the newer modalities available for the treatment of pulmonary hypertension introduced. By the end of the chapter, the reader should understand that patients with a single underlying autoimmune disease may present with one or more pulmonary manifestations and that different autoimmune diseases may present with similar pulmonary manifestations. This heterogeneity poses both diagnostic and treatment challenges, and many questions still remain regarding optimal treatment.     

Peripheral blood T-lymphocyte subsets in autoimmune thyroid disease.

Interest in T-lymphocyte subsets has arisen because of their involvement in the autoimmune process. Contradictory results have been published in the literature about the number of peripheral blood lymphocyte subsets in autoimmune diseases. In order to investigate the number and distribution of peripheral blood lymphocyte subsets in autoimmune thyroid disease, the levels of total T-lymphocytes (CD3), T-helper (CD4) and T-suppressor/cytotoxic (CD8) lymphocytes were determined in 44 patients with Graves' disease (1), multinodular goiter (2) and Hashimoto's thyroiditis (3). All patients had high levels of antithyroglobulin and thyroid antiperoxidase (antimicrosomal) antibodies. The T subset levels were related to the functional thyroid status, measured as serum free thyroxine (FT4) and thyrotropin (TSH). Our data show the existence of a strong influence of functional status on CD3, CD4 and CD8 levels, as reflected in the significant correlations obtained with FT4 (negative) and TSH (positive). A significant decrease in all populations was observed in Graves' disease hyperthyroid patients. A decrease in the CD4/CD8 ratio in Hashimoto's thyroiditis hypothyroid patients was observed, in contrast to an increase in the ratio in autoimmune hyperthyroid patients. This points to the CD4/CD8 ratio as a differential characteristic between the two autoimmune (hypothyroid and hyperthyroid) entities, independent of free thyroxine levels. No significant correlation was found between antithyroid antibody levels and peripheral blood T-lymphocyte subsets or serum levels of FT4 and TSH.     

Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura

Chronic autoimmune thrombocytopenic purpura (AITP) is associated with autoantibodies specific for platelet membrane components, often including glycoprotein GPIIIa. T helper (Th) cells reactive with GPIIIa, which are capable of driving the autoantibody response, are activated in AITP, and the aim here was to map the epitopes that they recognize. Peripheral blood mononuclear cells (PBMCs) were obtained from 31 patients with AITP and 30 control donors and stimulated with a panel of 86 overlapping synthetic 15-mer peptides spanning the complete sequence of GPIIIa. One or more peptides elicited recall proliferation by PBMCs from 28 of the patients, and, typically, multiple sequences were stimulatory. In contrast, responses in healthy control donors were rare (chi-square test = 115.967; P 相似文献   

Immunologic characterization of a helper T-cell lymphoma

The lymphocytes of a patient with a T-cell non-Hodgkin's lymphoma with peripheral blood involvement and polyclonal hypergammaglobulinemia were characterized in terms of surface markers and immunologic functions. Using the fluorescence-activated cell sorter and employing various monoclonal antibodies against T-cell surface antigens, it was shown that almost all of the patient's peripheral blood lymphocytes were positive for OKT4 and 9.3, antibodies that recognize helper T-cell subset. The circulating lymphoma cells had typical characteristics for T cells; they formed spontaneous rosettes with sheep erythrocytes and stained with the pan-T-cell antibodies 9.6 and 10.2, but did not react with other anti-T-cell monoclonal reagents such as OKT3, UCHT-1, and 3A1. The cells appeared to be mature by the fact that they did not stain with OKT6, and terminal deoxynucleotidyl transferase was undetectable. Functionally, they were able to provide "help" for antibody production, and they could be stimulated to produce moderate amounts of interleukin-2, while unable to proliferate in response to mitogens. Morphologically, some of the lymphocytes showed a deeply cleaved nucleus.     

Combination chemotherapy in a patient with severe multiple systemic autoimmune disease

We describe the occurrence of autoimmune haemolytic anaemia (AIHA) in a patient who had had both idiopathic thrombocytopenic purpura (ITP) and bullous pemphigoid (BP) for about 10 years. All of these diseases worsened rapidly, and the patient's clinical condition became critical after an episode of acute pneumonia. His AIHA, ITP and BP were responsive to combination chemotherapy consisting of cyclophosphamide, vincristine and prednisolone (CVP therapy).     

Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus. Correlation with clinical features

Immunoregulatory T-cell subsets as defined by differentiation antigens were studied in 32 patients with systemic lupus erythematosus (SLE) and 16 healthy persons using the monoclonal antibodies OKT 3 or anti-Leu 4 (T cells), anti-Leu 2a (suppressor/cytotoxic cells) and anti-Leu 3a (helper/inducer cells). Compared with the 95 percent confidence limits in control subjects, decreases or increases of Leu 3a+ cells were observed in 23 patients, whereas abnormal percentages of Leu 2a+ cells were observed in only 10 patients (p less than 0.002). The ratio of Leu 3a+ to Leu 2a+ cells varied over a much broader range (0.31 to 4.14) in patients with SLE than in control subjects (95 percent confidence limit 1.04 to 2.20). Furthermore, the helper:suppressor ratio correlated significantly (p less than 0.001) with a numerical clinical characterization of the patients. A low helper: suppressor ratio was observed in patients with severe renal disease, thrombocytopenia and onset of SLE by 20 years of age. Patients with a high helper:suppressor ratio had multisystem disease including lymphadenopathy, but only rarely SLE renal disease. Patients with a normal helper:suppressor ratio had the most widespread multisystem disease, often involving the kidneys and the central nervous system. The ratio was not correlated with duration of illness, disease activity or corticosteroid dosage in the patients examined. The study suggests that SLE is not one disease entity, but rather a symptom complex with different immunoregulatory abnormalities and associated manifestations.     

Distinct roles for jasmonate synthesis and action in the systemic wound response of tomato

Plant defense responses to wounding and herbivore attack are regulated by signal transduction pathways that operate both at the site of wounding and in undamaged distal leaves. Genetic analysis in tomato indicates that systemin and its precursor protein, prosystemin, are upstream components of a wound-induced, intercellular signaling pathway that involves both the biosynthesis and action of jasmonic acid (JA). To examine the role of JA in systemic signaling, reciprocal grafting experiments were used to analyze wound-induced expression of the proteinase inhibitor II gene in a JA biosynthetic mutant (spr-2) and a JA response mutant (jai-1). The results showed that spr-2 plants are defective in the production, but not recognition, of a graft-transmissible wound signal. Conversely, jai-1 plants are compromised in the recognition of this signal but not its production. It was also determined that a graft-transmissible signal produced in response to ectopic expression of prosystemin in rootstocks was recognized by spr-2 but not by jai-1 scions. Taken together, the results show that activation of the jasmonate biosynthetic pathway in response to wounding or (pro)systemin is required for the production of a long-distance signal whose recognition in distal leaves depends on jasmonate signaling. These findings suggest that JA, or a related compound derived from the octadecanoid pathway, may act as a transmissible wound signal.     

T-cell subsets in multiple myeloma

Summary Blood leukocyte and lymphocyte counts, absolute and relative numbers of T-lymphocytes and T-cell subsets were studied in 45 patients with multiple myeloma and 18 healthy controls. No differences were found between untreated patients and controls. In the group of untreated patients similar results were obtained in patients with low-intermediate tumour cell mass as in patients with large tumour cell mass. In patients with large tumour cell mass studied during cytostatic therapy, leukocyte and lymphocyte counts, T-cells, OKT4⁺ cells and OKT4/OKT8 ratios were significantly lower than in untreated patients. Patients studied at varying intervals (2–28 mo.) after cessation of therapy still exhibited abnormal leukocyte and lymphocyte counts, numbers of T-cells, OKT4⁺ cells and OKT4/OKT8 ratios.