Percentage Of T4 Research Articles

Autologous rosette forming cells in subjects at risk for the acquired immunodeficiency syndrome.

We investigated the distribution of autologous rosette forming cells (ARFC) in the peripheral blood from subjects at risk for the acquired immunodeficiency syndrome (AIDS). The mean percentage of ARFC with autologous plasma from 35 male homosexual individuals was significantly lower than that of 31 normal controls. The mean percentage of ARFC of SARA had a direct linear correlation with the percentage of T4+ cells (p less than 0.01). Within the SARA group, those with antibodies against HTLV-III/LAV had percentages of ARFC significantly lower than SARA with negative antibodies. Plasma from SARA decreased the percentage of ARFC of normal cells when compared to normal homologous plasma (p less than 0.005), whereas normal homologous plasma did not modify the low percentage of ARFC from SARA. These results indicate that SARA possess a depletion of this subpopulation of T cells. This is more pronounced in subjects with anti-HTLV-III/LAV antibodies. The low ARFC is related to a decrease in the number of cells that correlates with the number of T4+ cells. The inhibition of normal ARFC by plasma from SARA suggests the existence of plasma factors that could mask the lymphocyte receptors for their own red blood cells and/or coat erythrocytes preventing lymphocyte-erythrocyte binding.

Treatment of adult patients with idiopathic thrombocytopenic purpura with intravenous immunoglobulin: effects on circulating T cell subsets and PWM-induced antibody synthesis in vitro.

Eight adult patients with idiopathic thrombocytopenic purpura (ITP) were given two 5-d courses of intermediate (250 mg/kg body weight/d) to high dose (400 mg/kg body weight/d) intravenous infusions of human plasmin-cleaved Ig, at 15-30 d intervals. Three patients also were given single booster infusions (400 mg/kg body weight for 1 d) of a different preparation, S-sulfonated Ig. As expected, significant though transient rises in the platelet count were consistently observed in all patients. The mean platelet count increase was 95 600/mm3 after the first course, and 143 500/mm3 after the second course. Similar effects of lower magnitude were obtained several times in the patients given single booster doses. In three patients, platelet-bound IgG levels were decreased in association with Ig therapy. Phenotypic analysis of T cell subsets before starting Ig therapy and at the end of the second high dose course of intravenous Ig treatment revealed significant reductions in the proportion of T4+ lymphocytes in five patients and relative increases in the percentage of T8+ cells after therapy. As the overall proportion of T3+ cells remained unchanged, the T4+/T8+ ratio was therefore decreased. The total number of circulating lymphocytes was also decreased following therapy. In addition, PWM-driven Ig biosynthesis in vitro was significantly impaired after therapy in most patients, the capacity to synthesize IgG being mainly affected. It is concluded that, in addition to the reported transient blockade of the reticuloendothelial system, non-specific suppression of polyclonal Ig biosynthesis induced by the high dose Ig infusions also contributes to the net increase in platelet count.

Abnormalities of lymphocyte subsets and anti-LAV/HTLV-III status in Greek hemophiliacs.

Peripheral blood lymphocyte subsets and the incidence of LAV/HTLV-III antibodies were studied in 63 patients with hemophilia A who had been transfused with a low dose regimen of commercial (U.S.A.) factor VIII concentrates. Five patients with hemophilia B were also included in this study. In hemophilia A patients a significant reduction in the percentage and absolute numbers of T4+ cells and of the T4/T8 ratio and a significant increase in the percentage of T8+ and Leu-7+ cells were observed. These abnormalities were independent of the presence of anti-LAV/HTLV-III. In hemophilia B patients a significant increase of T8+ cells and a decrease of T4/T8 ratio was noted while the percentage of Leu-7+ cells was normal. A significant negative correlation of F VIII units transfused and T4/T8 ratio was seen only in LAV/HTLV (-) patients, suggesting that F VIII per se could cause immunodysregulation. Seropositive patients were found to have consumed a larger amount of F VIII units than seronegative patients during the period 1980-1984 (p less than 0.005).

Definite vs Adjuvant Radiotherapy: Comparative Effects on Lymphocyte Subpopulations in Patients With Head and Neck Squamous Carcinoma

The recent association of alterations in T-lymphocyte subpopulations and impaired cellular immunity prompted an investigation of the effects of radiotherapy (RT) on serial levels of lymphocyte subsets in 30 patients with head and neck squamous carcinoma. Percentage and absolute levels of T3, T4, T6, T8, T10, T11, and Leu 7 cells were measured before, during, and after RT at monthly intervals for six months and compared with levels in 40 normal subjects. Sixteen patients received curative and 14 postoperative adjuvant RT. Before treatment, mean subset levels were similar among the patient and normal groups except for elevated Leu 7 (natural killer) cells in patients with stage I and II disease. There were profound decreases in absolute levels of each subpopulation during and after RT. The percentage of T4 (helper/inducer) cells decreased, whereas that of T8 (cytotoxic/suppressor) and Leu 7 cells tended to increase. Compared with normal values, the mean T4/T8 ratio decreased significantly by six months after RT, when absolute levels of the subsets had rebounded to pretreatment levels in the definitive RT group but remained profoundly decreased in the adjuvant group. The differing recovery patterns suggest that factors other than RT may contribute to persistent immunosuppression following RT.

Lymphocyte phenotype and function in chronically transfused children with sickle cell disease.

Immunologic studies were performed on mononuclear cells from ten chronically transfused children with sickle cell disease, and the results were compared with those from five other groups: 21 sickle cell patients who were not receiving regular transfusions, 6 chronically transfused children with other forms of refractory anemia, 10 previously splenectomized children, 5 boys with hemophilia A, and 27 normal adult controls. The helper:suppressor T cell ratios (T4:T8) in all groups except hemophiliacs were normal, were unrelated to the number of units transfused, and were not suggestive of findings reported for patients with the acquired immune deficiency syndrome (AIDS) or groups at risk for the syndrome. Percentages of T3, T4, and T8 cells were low in sickle cell and splenectomized patients, but not in chronically transfused patients with other anemias. Serum IgG was frequently elevated, and IgG synthesis in vitro was increased relative to IgM synthesis in sickle cell patients. Coculture experiments indicated that such findings may stem from a selective increase in IgG synthesis by B cells. Thus, transfused sickle cell patients have a particular pattern of immunologic abnormalities that is distinct from that seen in AIDS.

939 PHENOTYPIC AND FUNCTIONAL CHANGES OF LYMPHOCYTES IN HEMOPHILIACS

Changes in cellular immunity have been reported in hemophiliacs receiving lyophilized factor concentrate, T cell subsets, mitogenic responsiveness, and degree of hypergammaglobulinemia in healthy hemophiliacs were examined in order to determine the effect of product therapy on immune responsiveness of children with hemophilia (age range, 3-21 years). The study population was comprised of 21 hemophilia A patients receiving factor VIII concentrate, 10 hemophilia A patients receiving cryoprecipitate, 8 hemophilia B patients receiving factor IX concentrate and 20 healthy children receiving no blood products. The percentage of T4+ lymphocytes was decreased in all hemophiliacs regardless of therapy (p<0.05). Only patients with hemophilia A receiving factor VIII concentrate exhibited a concomitant increase in the percentage of T8+ lymphocytes and showed a significantly decreased T4/T8 ratio (p<0.05). Depressed mitogenic responsiveness to phytohemagglutinin and concanavalin-A was observed in both hemophilia A and B patients receiving factor concentrate (p<0.05). No correlation was observed between changes in the T4/T8 ratio or mitogen responsiveness relative to the amount of product received. Hypergammaglobulinemia of the IgG class was demonstrable in all hemophilia groups and correlated with age (p<0.05). Phenotypic and functional alternations of lymphocytes demonstrated in hemophiliacs are probably the result of chronic factor exposure, which becomes more pronounced with increasing age.

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 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.

Suppressor Cells in End-Stage Renal Disease. Functional Assays and Monoclonal Antibody Analysis

Suppressor cell activity after concanavalin A induction was studied in peripheral blood mononuclear cells of patients undergoing long-term hemodialysis. Suppression both of the mixed lymphocyte reaction and of allogeneic cells stimulated with phytohemagglutinin was significantly higher with peripheral blood mononuclear cells from patients undergoing hemodialysis than with cells from control subjects. Expression of the Ia antigen on T lymphocytes (associated with immunologic activation) was studied by staining with monoclonal antibodies and two-color fluorescence analysis in a computer-linked cytofluorograph. In unstimulated cells, there was no significant difference between the patients and control subjects. After concanavalin A induction, the percentage of T4, and particularly of T8, cells expressing the Ia antigen was significantly higher in the group undergoing hemodialysis. The functional suppression seen after concanavalin A induction in the mixed lymphocyte reaction was significantly reduced by treatment with OKT8 monoclonal antibody and complement; in phytohemagglutinin cultures, both OKT8 and OKIa*1 antibodies were effective. The reduced in vitro response of uremic lymphocytes may thus be a consequence of increased suppressor activity associated with the T8-positive, Ia-positive subset of T cells.

Suppressor cells in end-stage renal disease: Functional assays and monoclonal antibody analysis

Suppressor cell activity after concanavalin A induction was studied in peripheral blood mononuclear cells of patients undergoing long-term hemodialysis. Suppression both of the mixed lymphocyte reaction and of allogeneic cells stimulated with phytohemagglutinin was significantly higher with peripheral blood mononuclear cells from patients undergoing hemodialysis than with cells from control subjects. Expression of the la antigen on T lymphocytes (associated with immunologic activation) was studied by staining with monoclonal antibodies and two-color fluorescence analysis in a computer-linked cytofluorograph. In unstimulated cells, there was no significant difference between the patients and control subjects. After concanavalin A induction, the percentage of T4, and particularly of T8, cells expressing the la antigen was significantly higher in the group undergoing hemodialysis. The functional suppression seen after concanavalin A induction in the mixed lymphocyte reaction was significantly reduced by treatment with OKT8 monoclonal antibody and complement; in phytohemagglutinin cultures, both OKT8 and OKIa ∗1 antibodies were effective. The reduced in vitro response of uremic lymphocytes may thus be a consequence of increased suppressor activity associated with the T8-positive, lapositive subset of T cells.

Wheat germ agglutinin decreases expression of the T8 antigen on human peripheral mononuclear cells.

We examined dynamics of expression of the human T-suppressor specific antigen, T8, following interaction of peripheral lymphocytes with wheat germ agglutinin (WGA). Cells were incubated at 37 degrees C with or without WGA (15 micrograms/ml) for 18 hrs, washed sequentially with N-acetylglucosamine (to remove bound WGA) and plain medium, then analyzed by flow cytometry for binding of lectins and monoclonal antibodies OKT8(T-suppressor specific) and OKT3 (pan-T specific). WGA pretreatment induced an overall 65% reduction in WGA binding and concomitant 30% reduction in percentage of T8+ cells. Furthermore, residual T8+ cells showed 50% reduction in T8 expression. Taking into account reductions in both percentages of T8+ cells and also antigen densities, WGA reduced T8 expression by greater than 60% overall. By contrast, binding of OKT3 and the lectins, concanavalin A (con A) and Ricinus communis agglutinin (RCA-I), was unaffected by WGA. The decreased T8 expression could not be explained by residual cell bound WGA and was fully reversible within 48 hours of removal of cells from WGA-containing medium. Therefore, WGA caused downregulation of T8 antigen expression. The effect of WGA was time- and concentration-dependent. Downregulation did not occur at 4 degrees C nor in the presence of azide, thereby demonstrating a requirement for cellular metabolism. The data suggest that WGA may bind to the T8 antigen, and they provide the possibility that similar downregulation of T8 by WGA may underlie certain of the in vitro immunoregulatory effects of this lectin.

Changes in T-lymphocyte subsets during childhood Epstein-Barr virus infectious mononucleosis.

Lymphocyte subsets were measured using monoclonal antibodies in 11 children with Epstein-Barr virus-induced infectious mononucleosis and compared with those of 10 normal children. In acute infectious mononucleosis the percentage of T8+ lymphocytes was greater while the percentage of T4+ lymphocytes and the T4+ to T8+ ratio were less than those measured in normal children. The percentage and absolute number of T lymphocytes, as enumerated by E rosetting, did not differ from the values for normal children. The children with acute infectious mononucleosis had a somewhat lower T8+ response than that observed in four adult infectious mononucleosis patients. With clinical recovery, the T lymphocyte-subset values returned toward normal. T8+ lymphocytes, a phenotype subset with predominantly suppressor activity, presumably reduce normal cellular immune functions transiently and may limit the continued proliferation of Epstein-Barr virus-infected B lymphocytes.

Alterations in immunoregulatory T cell subsets in active systemic lupus erythematosus.

To determine whether imbalance among subsets of human T cells exists in patients with systemic lupus erythematosus (SLE), we analyzed peripheral blood lymphocytes in SLE patients during active and inactive stages of disease. For this analysis, we used monoclonal antibodies to the surface antigens of inducer (T4) and suppressor (T5/T8) T cell subsets, as well as a common T cell antigen (T3). In contrast to normal and inactive SLE patients, the percentage of T3+ cells was reduced in all active SLE patients. More importantly, there was a selective decrease in T5+/T8+ suppressor T cells in 12 of 14 active patients, including 1 of 2 patients with drug-induced SLE. Serial analysis of three SLE patients showed a significant correlation between the presence of T5+/T8+ subset and clinical disease activity in all patients. We conclude that aberrations in suppressor T cell subsets are an important correlate of disease in patients with SLE.

Changes of the hypothalamus-pituitary-thyroid axis in streptozotocin-diabetic rats during adaptation to a low iodine diet.

ABSTRACT Studies on the hypothalamus-pituitary-thyroid axis have been carried out in control and in diabetic male Wistar rats during adaptation to a 125I-labelled low iodine diet. Diabetes was induced by a single streptozotocin injection (7 mg/100 g body weight). Thyroid weight, thyroid 127I and 125I content, [125I]iodoamino acid distribution in thyroid digests, plasma PBI, plasma and pituitary TSH and hypothalamic TRH by radioimmunoassay were measured between 5 and 30 days after saline or streptozotocin injection, corresponding to 15 and 40 days after onset of the 125I-LID. As compared to controls, diabetic animals have smaller thyroids. The 125I and 127I in diabetic thyroids between 5 and 10 days was lower than in control glands; at longer intervals both 125I and 127I increased with time in diabetics, while no remarkable changes were seen in the control glands. Furthermore, the percentage of T3 and the MIT/DIT and T3/T4 ratios in thyroids of diabetic were lower than in the corresponding control group at all intervals. These results are compatible with a deficiency of TSH stimulation and/or with a high thyroidal iodine content. Compared to the controls, each group of diabetic rats presented a significantly lower plasma TSH concentration, in spite of the fact that its plasma PBI is more or similarly reduced in diabetic than in controls. Furthermore, the decreased pituitary TSH secretion in diabetic rats at early intervals is lower than in controls although the pituitary TSH and hypothalamic TRH remain within normal ranges. It is concluded that the decrease in pituitary TSH secretion may be the result of a reduction of pituitary TRH stimulation, secondary to a diminished secretion and/or synthesis of TRH by the hypothalamus.

Quantitative determination of total and free triiodothyronine and thyroxine.

A new method for the quantitative determination of free triiodothyronine (fT3) and an accurate method for the quantitative determination of free thyroxine (fT4) in human plasma were developed. The percentages of T3 and T4 in plasma were studied by thin-layer chromato-graphy. An elutable fraction (EF) of T3, ratio of free 125I-T3 to protein-bound 125I-T3, was obtained using Sephadex-microcolumn chromatography. EF of T4 was obtained by the same method. Mean normal total T3 (tT3) and total T4 (tT4), calculated from plasma butanol-extractable iodine (BET) and molar percentages of T3 and T4, were 0. 63 and 5. 59mg per 100ml plasma, respectively. Mean normal fT3 and fT4, calculated from tT3, tT4 and EF values of T3 and T4, were 2.43 and 2.21mμg per 100ml plasma, respectively. The fT3 values can be obtained by the present method more easily and speedily than by the method of Nauman et al. The present fT4 values, in consideration of BET and the percentage of T4 in plasma, represent a more accurate one than the earlier data by Lee et al.