Phenotype study of blood T lymphocytes in alcoholic hepatopathies

Peripheral blood T lymphocytes and T lymphocytes subsets have been quantified by an indirect immunofluorescence technique using monoclonal antibodies, in 10 patients with fatty liver, 8 with acute alcoholic hepatitis (AAH), 10 with inactive cirrhosis and 7 with cirrhosis and AAH. Twenty normal subjects were studied as controls. As compared to controls (1.81 +/- 0.56 10(9)/l), we found a reduced number of peripheral T lymphocytes (OKT3+) in patients with inactive cirrhosis (0.98 +/- 0.45, p less than 0.001) and in patients with cirrhosis and AAH (1.22 +/- 0.51, p less than 0.02). The OKT4 to OKT8 ratio was normal in patients with fatty liver or inactive cirrhosis, but it was significantly higher in patients with AAH with or without cirrhosis (2.83 +/- 0.79, p less than 0.01, and 2.10 +/- 0.56, p less than 0,02, respectively) than in controls (1.68 +/- 0.24). In both groups, this increased ratio was due to a decreased proportion of OKT8+ circulating lymphocytes (19.2 +/- 6.7 p. 100, p less than 0.01, and 21.8 +/- 4.6 p. 100, p less than 0.02, respectively) when compared to controls (27.1 +/- 4.1 p. 100). The T-cell imbalance observed in patients with liver cell necrosis may be of importance in the pathogenesis of alcoholic liver disease.     

High levels of serum soluble interleukin-2 receptors in hyperthyroid patients: correlation with serum thyroid hormones and independence from the etiology of the hyperthyroidism

The serum levels of soluble interleukin-2 receptors (s-IL-2R) and soluble CD8 antigens (s-CD8) were measured in 33 patients with Graves' disease (GD), 29 with toxic nodular goiter (TNG), 6 with toxic adenoma (TA), and 12 with hypothyroidism, as well as in 11 patients with infectious mononucleosis (known to have high s-IL-2R and s-CD8 levels) and 34 normal controls. Serum levels of T3 and T4, both total and free, and of TSH were simultaneously determined. s-IL-2R levels were significantly higher in all patients with hyperthyroidism (mean +/- SD, 3276 +/- 1273 U/mL for GD, 4183 +/- 1832 for TNG, and 1671 +/- 648 for TA) compared to normal control values (P less than 0.001 for GD and TNG and P less than 0.01 for TA), while in the euthyroid state they were within the normal range (535 +/- 240 U/mL). Hypothyroid patients had significantly lower s-IL-2R levels compared to normal controls (P less than 0.05). A positive correlation (P less than 0.001) between serum s-IL-2R levels and total/free T3-T4 levels was found in these groups of patients, while no correlation between s-CD8 levels and s-IL-2R/T3/T4 was found. These findings suggest an association between hyperthyroxinaemia and activation of human lymphocytes in vivo.     

Suppressor cell function and T lymphocyte subpopulations in peripheral blood of patients with progressive systemic sclerosis

Three different in vitro assays--immunofluorescence with monoclonal anti-T cell reagents, enumeration of T gamma cells, and nonspecific suppressor cell function--were used for the analysis of suppressor lymphocytes in the circulation of 28 patients with progressive systemic sclerosis (PSS, scleroderma) and 20 normal individuals. Both OKT8+ and T gamma lymphocytes were significantly reduced (P less than 0.001 and P less than 0.02, respectively) in patients with PSS compared with controls. The OKT4/OKT8 ratio was increased (P less than 0.02). However, the mean suppressor cell index (SCI) of 1.9 (range 0.4-6.6) for patients with PSS was not significantly different (P greater than 0.05) from the SCI of 2.9 (range 1.2-14) for controls. Eleven of the patients had depressed suppressor cell function as indicated by the index value of less than 1.2. In only 5 of these patients, simultaneously measured T gamma and OKT8+ cells were reduced and OKT4+ lymphocytes were concomitantly increased. There were no significant correlations between the numbers of T gamma or OKT8+ cells and the SCI in patients and controls. Neither depressed suppressor cell function nor the OKT4+/OKT8+ ratio greater than 4.2 (greater than 2 SD of normal) in the patients could be related to other immunologic findings, to disease duration and severity, or to involvement of internal organs. These results suggest that depressed suppressor cell activity and immunoregulatory T cell imbalance in PSS may not be directly related to the pathogenesis of the disease.     

Peripheral T-lymphocyte subpopulations in primary and alcoholic dilated cardiomyopathy

In order to test the hypothesis of the role of a suppressor/cytotoxic T lymphocyte deficit in the pathogenesis of dilated cardiomyopathies (DCM), 20 patients (11 alcoholic-A; 9 primary-P) were compared with 24 normal controls (N) and 10 patients with chronic cardiac failure (CCF). The percentage of OKT 3, a global assessment of the T lymphocytes, did not differ significantly between the groups. The percentage of OKT 4 (helper T lymphocytes) was significantly lower in DCM (43 +/- 8.1 p. 100) compared to N (51.92 +/- 8.1 p. 100), p less than 0.001. The percentage of OKT 4 was also lower in CCF (45.3 +/- 3.91 p. 100) compared to N (p less than 0.05). There was a very significant decrease in the percentage of OKT 8 (suppressor/cytotoxic T lymphocytes) in DCM (17.23 +/- 4.78 p. 100) compared to N (26.42 +/- 5.72 p. 100) (p less than 10(-8)). A reduction of OKT 8 was also observed in CCF compared to N (p less than 0.05). The ratio of OKT 4/OKT 8 was significantly higher in DCM (2.7 +/- 0.97) compared to N (2.08 +/- 0.6) (p less than 0.05). This difference was not observed in CCF (2.19 +/- 0.48). There were no differences between DCM A and P. These results indicate that chronic cardiac failure is associated with an equal reduction in the percentage of OKT 4 and OKT 8 lymphocytes. Dilated cardiomyopathy is associated with a large reduction in the OKT 4 and especially in the of OKT 8 with a statistically significant increase in the OKT 4/OKT 8 ratio. Although chronic cardiac failure seems to affect lymphocytes, these results are compatible with a deficit of suppressor/cytotoxic T lymphocytes in dilated cardiomyopathies.     

Analysis of T lymphocytes after bone marrow transplantation using monoclonal antibodies

Using monoclonal antibodies to cell surface antigens and fluorescent cell sorter analysis, we studied peripheral blood lymphocyte subsets after bone marrow transplantation (BMT). In 13 patients studied 3 mo or more after BMT, the ratio of T-cell subsets defined by antibodies OKT4 and OKT8 was reversed (OKT4/OK%8 = 0.7 +/- 0.3) in comparison to normal volunteers or bone marrow donors (ratio OKT4/OKT8 = 1.7 +/- 0.4) (p less than 0.001). This reversed ratio persisted for up to 3 yr after BMT. In contrast to a previous report, presence of an abnormal ratio of T-cell subsets did not correlate with clinically significant graft- versus-host disease (GVHD). In agreement with a previous study, (26% +/- 8%; less than 4% in normals (p less than 0.001) and antibody OKT10 reactive cells (39% +/- 20% versus 10% +/- 4%) (p less than 0.01), suggesting in vivo activation. However, their PBL did not react with antibody B3/25 (antitransferrin receptor), a marker found on normal PBL after in vitro activation by mitogens (BMT patients less than 5%; normal PBL T cells plus PHA 45% +/- 11%). These results demonstrate that BMT patients have: (A) an abnormal ratio of T-cell subsets in the presence or absence of clinically significant GVDH disease so that these measurements were not useful in monitoring patients; (B) an increased number of T cells with cell surface phenotype (OKT8+, Ia+, OKT10+, B3/25-) that is distinct from normals but similar to patients with infectious mononucleosis or acquired hypogammaglobulinemia.     

SERUM CONCENTRATION OF UNSATURATED THYROXINE-BINDING GLOBULIN IN HYPER- AND HYPOTHYROIDISM

The concentration of serum thyroxine (T4)-binding globulin (TBG) not binding T4 (unsaturated TBG, u-TBG) was determined in hyper- and hypothyroidism. u-TBG was expressed as the product of TBG concentration and the ratio of free TBG capacity to maximal TBG capacity as determined by reverse-flow electrophoresis. u-TBG concentration in normal sera (n = 40) was 15.5 +/- 2.3 mg/l (mean +/- SD), or 257 +/- 38 nmol/l for a molecular weight of TBG of 60 000 daltons. u-TBG levels were significantly lower in hyperthyroidism (7.1 +/- 2.3 mg/l, n = 16, P less than 0.001) and higher in hypothyroidism (21.7 +/- 5.0 mg/l, n = 22, P less than 0.001). Based on partial correlation analysis, u-TBG was inversely correlated to serum T4 (r = -0.586, P less than 0.001), but not correlated to triiodothyronine (T3) (r=-0.180, NS). There was a reciprocal correlation between u-TBG concentration and the T3 uptake value (r = 0.748, P less than 0.001). There was also a reciprocal correlation of u-TBG with both % free T4 (r = 0.425, P less than 0.001) and % free T3 (r = 0.377, P less than 0.001), when the data were subjected to partial correlation analysis. These results provide the values for u-TBG concentration in hyper- and hypothyroidism, and support the concept that the free fractions of serum thyroid hormones may be determined by the number of binding sites of the TBG molecule that are not saturated with T4 in hyper-and hypothyroidism.     

Enumeration of absolute numbers of T lymphocyte subsets in B-chronic lymphocytic leukaemia using an immunoperoxidase technique: relation to clinical stage

An immunoperoxidase technique has been used to identify and enumerate helper and suppressor T-cell subsets, as defined by reactivity with Coulter T4 and OKT8 monoclonal antibodies in 54 patients with B chronic lymphocytic leukaemia (B-CLL) and in the same number of matched controls. The ratio of T4+ to T8+ cells was significantly reduced in the B-CLL group as a whole (P less than 0.001) and in each stage of the three clinical staging systems. There was an increase in the median absolute level of T8+ cells in the whole CLL group (P less than 0.001). However, subdivision of the CLL group by clinical staging systems revealed a large group (28 patients) in which median T8+ cell levels were not raised and median T4+ cell levels were low (P less than 0.01). There was no significant decrease in T4+:T8+ ratio, increase in T8+ cells or decrease in T4+ cells with progression of clinical stage. Absolute numbers of E+ cells were significantly raised in all staging systems as were E+ T4- T8- cells (P less than 0.001). A significant alteration in either of these populations with progression of clinical stage was not present.     

Peripheral blood lymphocyte subpopulations in polycythaemia and thrombocythaemia

Lymphocyte subpopulations from peripheral blood of normal subjects and patients with primary proliferative polycythaemia (PPP), idiopathic erythrocytosis (IE) and essential thrombocythaemia (ET) were separated using antihuman immunoglobulin antiserum for B lymphocytes and the following monoclonal antibodies: OKT3, directed against the general T-lymphocyte subpopulation, OKT4 and OKT8, detecting respectively T-helper and T-suppressor lymphocyte subpopulations, OKM1 reacting mainly with monocytes. A decrease in the number of OKT3+ cells was observed both in PPP and IE, with a particular fall of the OKT8+ (suppressor) cells, so that the T4/T8 ratio was significantly increased (P less than 0.03 in PPP and P less than 0.0005 in IE). The ratio remained normal in samples from ET. OKM1+ cells were significantly increased in PPP (P less than 0.04), but not in IE, while in ET there was a rise in a few cases only. The present data point out some definite changes in the circulating lymphomonocytic cell subsets, which may be of interest in the study of this group of myeloproliferative disorders.     

Analysis of T cell subsets in cancer patients treated with interferon

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.     

Study of IgE and T lymphocyte subsets in patients with serious bronchial asthma

In the present study, 30 patients with serious asthma were selected for the investigation of IgE and T lymphocyte subsets in PBL. By the indirect McAb immuno-SPA assay, it was observed that the percentages of OKT3 and OKT8 but the percentage of OKT4 subset and T4/T8 ratio were significantly higher than those of normal persons (P less than 0.01). The total IgE in serum of patients (performed by ELISA) was also much higher than that of normal persons (P less than 0.05). In addition, there was a closed relationship between the level of IgE and the percentage of OKT of the patients (r = 0.37369, P less than 0.05). The results indicated that one of possible reasons of higher IgE in serum of asthma patients was the abnormality of T lymphocyte subsets in vivo.     

T cells in monoclonal gammopathies

Subpopulations of human T lymphocytes were analysed by monoclonal antibodies (OKT3, OKT4, OKT8) in healthy controls and in patients with multiple myeloma (MM), Waldenstr?m's macroglobulinemia (WM) and benign monoclonal gammopathy (BMG). Lymphocytes forming rosettes with SRBC correlated well with T cells staining in indirect immunofluorescence by OKT3 monoclonal antibodies. The relative and absolute numbers of OKT4+ T cells were significantly lower in patients than in controls. Though, the percentage of OKT8+ T cells was increased in patients, the total OKT8+ cell counts were normal in all patient groups. The ratio between OKT4+ and OKT8+ lymphocytes was low in the groups of treated MM and of WM patients compared to controls (P less than 0.001). Moreover, the ratio was lower than the normal range in 27% of BMG and 38% of untreated MM patients. The imbalance between OKT4+ and OKT8+ T cells in untreated MM was more pronounced in clinical stage III patients than in stage I and II patients. The most pronounced changes were noted in treated MM patients. The significance of the altered T cell subsets in monoclonal gammopathies with regard to polyclonal and tumor B cell regulation remains to be established.     

Decreased 5'' nucleotidase activity in lymphocytes from asymptomatic sexually active homosexual men and patients with the acquired immune deficiency syndrome

5' Nucleotidase (5'NT) is an ectoenzyme associated with the plasma membrane of most mammalian cells. Low 5'NT activity has been observed in peripheral blood lymphocytes from patients with immunodeficiency states. 5'NT activity was measured in null and T-enriched lymphocytes from asymptomatic homosexual men and from 20 men with various degrees of the acquired immune deficiency syndrome (AIDS). Asymptomatic homosexuals were self-referred because of their concern about AIDS and were not necessarily representative of homosexuals in the general population. Enzyme activity was significantly decreased in both null (7.0 +/- 2.4 nmol/10(6) cells/h) and T-enriched (12.0 +/- 6.0 nmol/10(6) cells/h) lymphocytes in homosexuals as compared to lymphocytes from aged-matched heterosexual male and female controls (null = 10.8 +/- 6.5 and T = 22.3 +/- 10.6, P less than .0001 and .008, respectively). Decreased activity was present regardless of whether the patients were asymptomatic, had prodromal symptoms such as fever, lymph node enlargement, weight loss and diarrhea, or had opportunistic infections or Kaposi's sarcoma. Homosexuals had a significantly higher fraction of lymphocytes expressing the activation antigens T10 (20% +/- 3.3%) and Ia (13% +/- 2.9%) than controls (11% +/- 1.8% and 5% +/- 0.8%, respectively, P less than .05). They also had a significantly lower fraction of OKT4-positive helper lymphocytes than controls (22% +/- 3.4% v 35% +/- 2.2%, P less than .05). 5'NT activity in lymphocytes enriched for null cells from homosexuals correlated inversely with the percentage of Ia-positive lymphocytes (r = -.655; P less than .02). There was no correlation between 5'NT activity and the percentage of T4- or T8-positive lymphocytes or the T4/T8 ratio. Moreover, 5'NT activity was significantly decreased in both OKT4 (P less than .025) and OKT8 (P less than .05) enriched lymphocytes in homosexuals compared to controls. The data suggest that decreases in 5'NT may be a generalized defect of the peripheral blood T lymphocytes from active homosexuals that is independent of increases or decreases in specific T subpopulations or clinical status. It may contribute to the pathogenesis of AIDS.     

Decreased level of suppressor/cytotoxic T cells (OKT8+) in polymyalgia rheumatica and temporal arteritis: relation to disease activity

Separated peripheral blood mononuclear cells were analyzed by fluorescent microscopy with monoclonal antisera for T cells (OKT3+), helper/inducer T cells (OKT4+) and suppressor/cytotoxic T cells (OKT8+). Thirty-seven patients with polymyalgia rheumatica (PMR), 13 of whom had positive biopsies for arteritis, were studied and compared with 25 age and sex matched normal subjects. The percentages of OKT3+ and OKT4+ T cells were similar in the PMR group and controls, but percentage of OKT8+ T cells was significantly reduced in patients (14.8 +/- 6.8) compared with controls (22.1 +/- 6.3). Values of OKT8+ T cells were extremely low in untreated patients with active, acute disease (7.8 +/- 4.4%) and significantly lower than in prednisone treated patients with inactive disease (17.3 +/- 5.9). These findings indicate that low values of circulating OKT8+ T cells is a feature of PMR and is related to disease activity.     

Abnormalities of peripheral blood T lymphocyte subsets in polymyalgia rheumatica

The T lymphocyte subsets were studied by monoclonal antibodies in the blood of eight patients with polymyalgia rheumatica. The percentages of circulating T cells (OKT3+) were lower when compared with normal controls (p less than 0.02), as were the proportions of suppressor/cytotoxic (OKT8+) T cells (p less than 0.001), whereas the proportions of helper/inducer (OKT4+) T lymphocytes were not changed. Consequently, the OKT4:OKT8 ratio was higher in patients with polymyalgia rheumatica than in controls (p less than 0.001). On the contrary, circulating B cells were not altered. The decrease in peripheral blood OKT3+ and OKT8+ lymphocyte subsets suggests that there is an impairment of cell-mediated immunity in polymyalgia rheumatica.     

T-lymphocyte subpopulations in rheumatoid arthritis. II. Definition by monoclonal antibodies

Samples of peripheral blood of 27 patients with seropositive rheumatoid arthritis (RA) and 27 healthy age- and sex-matched controls were coded and studied for lymphocyte subpopulations. Monoclonal antibodies and indirect immunofluorescence were used to analyse subpopulations of purified T cells: OKT3 reacts selectively with all peripheral human T cells, OKT4 defines the helper/inducer subpopulation and OKT8 the suppressor/cytotoxic T cells. RA patients had a significantly lower relative lymphocyte count (p less than 0.001). whereas the percentage of all T cells was similar in patients and controls, RA patients had a significantly higher proportion of helper/inducer cells (62 +/- 1.3 vs. 56 +/- 1.0, p less than 0.005) and significantly decreased suppressors/cytotoxic cells (25 +/- 1.5 vs. 32 +/- 1.0; p less than 0.001). This resulted in an increased "immunoregulatory ratio" of helper to suppressor cells in RA patients (2.68 +/- 0.17) compared to their normal controls (1.83 +/- 0.10; p less than 0.001). The proportions of T cells expressing HLA-D-like antigens (defined by a monoclonal antibody to human Ia) was not different in patients and controls. These findings confirm conclusions derived from our previous study of T cell subsets defined by the expression of Fe-receptors (Tm and Tg), that in the peripheral blood of patients with RA, helper mechanisms predominate over suppressor mechanisms. This derangement of the immunoregulatory balance may have an important role in the pathogenesis of seropositive RA.     

Cytochemistry of normal lymphocyte subsets defined by monoclonal antibodies and immunocolloidal gold

The cytochemical reactivities of 3 acid hydrolases, alpha-naphthyl acetate esterase (ANAE), acid phosphatase and beta-glucuronidase were investigated in normal peripheral blood lymphocyte subsets defined by monoclonal antibodies OKT3, 4, 8 and FMC4 (anti-Ia). A combined monoclonal antibody-immunocolloidal gold/cytochemical staining procedure was used to determine enzyme activities and distributions of reaction product in each subset. Cytochemical profiles for each lymphocyte subset were defined. The majority (greater than 85%) of T cells (OKT3+) were positive for all 3 enzymes whereas a minority (less than 40%) of B cells (FMC4+) displayed reactivity. The cytochemical profiles of T helper/inducer (OKT4+) and T suppressor/cytotoxic (OKT8+) cells were not significantly different and corresponded to that observed for OKT3+ cells; thus none of these enzymes can be used to distinguish normal lymphocyte subsets cytochemically. ANAE reactions were further analysed, in the respective subsets, on the basis of dot-like or scattered/diffuse reactivity. The ratios of cells displaying dot-like: scattered/diffuse reactivity, in the respective subsets, were OKT3+, 5.4:1; OKT4+, 8.1:1; OKT8+, 2.4:1; FMC4+, 0.4:1. The cytochemical profiles and ANAE reactivities of T cell subsets identified by monoclonal antibodies differ from those displayed by T cell subsets defined by Fc receptors and confirms that there is little correlation between subsets defined by these two methods.     

T-cell subpopulations in patients with monoclonal gammopathies: essential monoclonal gammopathy, multiple myeloma, and Waldenstrom macroglobulinemia

T-cell subsets defined by monoclonal antibodies (OKT3, OKT4, and OKT8) were analyzed in 117 patients with monoclonal gammopathies--69 multiple myeloma (MM) (30 untreated and 39 treated), 14 Waldenstr?m's macroglobulinaemia (WM), and 34 essential monoclonal gammopathy (EMG) patients. The percentage and absolute numbers of total T-lymphocytes (E+, OKT3+ cells) were within the normal range in all groups except for the treated MM patients, in which a decrease in the absolute number could be observed. The percentages of OKT4+ cells were significantly lower in MM (35 +/- 1.7) than in EMG patients (43 +/- 2) and controls (50 +/- 2). In contrast, OKT8 cells correspondingly increased in MM (38 +/- 1.6) compared with EMG patients (29 +/- 1) and controls (27 +/- 1). The OKT4/OKT8 ratio was lower in MM than that in EMG patients and controls (p less than 0.01) and was shown to be one of the four most significant variables in a linear discriminant analysis used to distinguish between MM and EMG groups. The MM patients in clinical stage III as well as Bence-Jones myeloma patients showed a more pronounced OKT4/OKT8 imbalance. The treatment did not influence the percent distribution of T-cell subpopulations. The patients with WM exhibit an alteration in the distribution of the T-cell subsets similar to the MM patients with a T4/T8 ratio of 1.1 +/- 0.1. This imbalance was more pronounced in WM patients with monoclonal B-lymphocytes in peripheral blood (leukaemic phase of WM). The functional significance of the altered T-cell subsets in MM and WM patients remains to be established, though it is probable that such an imbalance plays an important role in regulating these B-cell proliferations.     

Use of adjunctive potassium iodide after radioactive iodine (131I) treatment of Graves' hyperthyroidism

One hundred and nineteen patients with Graves' hyperthyroidism who were treated with 131I alone or 131I followed by potassium iodide (131I + KI) were studied retrospectively. Patients in both groups who required only a single dose of 131I for successful treatment of hyperthyroidism had similar age, gland size, 24-h radioactive iodine uptake, pretreatment serum T4 concentrations, and radioactive iodine treatment dose. Seven weeks after 131I, mean serum T4 concentrations were 12.3 +/- 6.1 micrograms/dl (mean +/- SD) in patients who received 131I alone and 8.0 +/- 3.9 micrograms/dl in patients who received 131I + KI (p less than 0.001). Sixty percent of the patients who received 131I + KI and remained euthyroid 1 yr after 131I treatment developed documented transient hypothyroidism while receiving KI (serum T4, 1.4 +/- 0.9 micrograms/dl). Patients with transient hypothyroidism receiving KI had larger estimated thyroid gland weights when hypothyroid than patients whose hypothyroidism was permanent (32 +/- 6 vs. 16 +/- 11 g; P less than 0.001). The overall incidence of hypothyroidism 1 yr after treatment with 131I was 58% in each of the two groups. Sixteen percent of each group were not successfully treated by a single dose of 131I and required further therapy. Adjunctive KI effectively treated thyrotoxicosis more rapidly than 131I alone without adversely affecting outcome at 1 yr; however, patients taking KI more often develop transient hypothyroidism.     

Changes of peripheral mononuclear cell subpopulations in autoimmune thyroid diseases

To estimate abnormalities in humoral or cellular immunity that relate to the etiologies of Graves' disease (GD) and Hashimoto's thyroiditis (HT), peripheral mononuclear cell subpopulations were enumerated by an immunofluorescence technique using monoclonal antibodies. Also antithyrotropin receptor antibodies (thyrotropin-binding inhibitor immunoglobulin, TBII) were measured by the radioreceptor assay according to Smith's method; and antithyroglobulin antibodies (TGHA) and antithyroid microsomal antibodies (MCHA), by the tanned red cell hemagglutination technique. The data obtained were analyzed for the count of peripheral total white cells, lymphocytes and granulocytes, and to the level of serum free thyroxine (T4), free T4 index (FT4I) and free triiodothyronine index (FT3I). Peripheral white cells tended to be decreased in some cases of GD and HT. The absolute count of lymphocytes was slightly increased in GD but did not change in HT. On granulocytes (neutrophils mainly), the absolute count was considerably decreased in hyperthyroid GD. In this disease, FT3I showed significantly positive correlations to the percentage and absolute count of peripheral lymphocytes, whereas FT4I revealed significantly negative correlations to the percentage and count of granulocytes. These facts indicate that lymphocytosis and granulocytopenia in GD might be ascribed partially to the direct effects of thyroid hormones. The percentage of peripheral OKT3-positive cells (common T lymphocytes) was significantly decreased in untreated cases of GD, showing negative correlations to FT4, FT4I and FT3I. The absolute count of OKT4-positive cells (inducer/helper T lymphocytes) was increased in untreated cases of GD and hyperthyroid and euthyroid cases receiving antithyroid drugs (ATD) for GD. But peripheral OKT8-positive cells (suppressor/killer T lymphocytes) was significantly decreased in HT. The percentage of peripheral OKT8-positive cells in GD was also decreased in untreated and remitted cases, but slightly more increased in ATD-medicated cases than in nonmedicated cases. The ratios of OKT4-positive cells to OKT8-positive cells (OKT4+/OKT8+ ratios) were significantly increased in untreated, ATD-medicated euthyroid and remitted cases of GD, and in HT. It seems that ATD may exert direct effects on OKT8-positive cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

T lymphocyte subpopulations in chronic lymphocytic leukemia of B cell type in relation to immunoglobulin isotype(s) on the leukemic clone and to clinical features

Total blood T lymphocytes and subpopulations (OKT4+ and OKT8+ cells) were studied in 59 patients with B cell chronic lymphocytic leukemia (B-CLL). In 48 previously untreated patients, total T lymphocytes were higher as compared to healthy controls (p less than 0.001). T-cells and OKT8+ cells were significantly increased in patients in advanced clinical stage and with progressive disease in comparison to patients with low stage and indolent disease. High numbers of OKT8+ lymphocytes were also seen in patients with a dominance of mu heavy chains on the leukemic clone. Moreover, in this patient group the OKT8+ subpopulation correlated with total B cells (r = 0.68, p less than 0.001) while in patients with a mu delta phenotype no such correlation was seen. After successful cytostatic therapy there was a reduction in total numbers of both OKT4+ and OKT8+ cells, in particular, with a concomitant increase in OKT4/OKT8 ratios.