OKT8-positive Cells Research Articles

Phosphodiesterase Inhibition by Ro 20-1724 Reduces Hyper-IgE Synthesis by Atopic Dermatitis Cells In Vitro

Peripheral blood mononuclear leukocytes (MNL) from patients with atopic dermatitis spontaneously produce large amounts of IgE in vitro. These cells also show markedly elevated levels of cAMP phosphodiesterase (PDE) which may be responsible for the observed abnormal cAMP responsiveness. Treatment of atopic dermatitis MNL with varying concentrations of the cAMP PDE inhibitor Ro 20-1724 resulted in progressively decreasing amounts of IgE synthesis, statistically significant at the 10(-4) M and 10(-5) M concentrations. There was a close correlation between PDE inhibition and inhibition of IgE synthesis, r = 0.93, p less than 0.05. To define the cellular target of the drug, we used monoclonal antibodies directed toward MNL subsets (Lyt 3, OKT8, OKT4, monocyte-myeloid) in a modified "panning" method to perform experiments with purified subsets. With untreated subsets, removal of OKT4-positive cells significantly reduced IgE synthesis; readdition of OKT4-positive cells enhanced IgE synthesis. OKT8 cells and monocytes did not affect IgE synthesis. Pretreatment of T cell-depleted MNL with Ro 20-1724 resulted in significantly more inhibition of IgE synthesis than did pretreatment of T enriched cells prior to recombination with the reciprocal untreated subset and subsequent culture. Similarly, pretreatment of monocyte-depleted cells resulted in significantly more inhibition of IgE synthesis than pretreatment of monocyte-enriched cells prior to recombination and culture. The majority of the effect appeared to be mediated by a direct effect on the B cells. However, some inhibition of IgE synthesis was also achieved through pretreatment of T enriched cells. Since pretreatment of isolated suppressor/cytotoxic or helper/inducer T-cell subsets did not give the same degree of inhibition as with unfractionated T cells, a T-T interaction may be involved in this aspect. The imidazolidinone derivative, Ro 20-1724, significantly and consistently inhibited both the elevated cAMP phosphodiesterase activity and the elevated spontaneous IgE synthesis of MNL from patients with atopic dermatitis. These findings demonstrate a previously undescribed link between cAMP PDE levels and in vitro IgE synthesis.

Biology of human epidermal Langerhans cells: cell cycle studies.

Langerhans cells (LC) are considered to play an important role in the initiation of the immune response in the skin. This study was performed to analyse the kinetics of LC in normal human epidermis. Using flow cytometry (FCM), we have applied three methods to estimate LC DNA distribution: FCM DNA measurement in LC-enriched suspensions (70-90% purity), FCM-correlated analysis of DNA and OKT6-positive cells in original epidermal cell suspensions, and staining of LC-enriched suspensions by the Feulgen technique on microscopic slides and counter labelling of contaminating keratinocytes with anti-keratin antiserum to eliminate them from the LC DNA estimation. All three methods clearly showed that human LC are a cycling cell population, and it was suggested that LC may represent a stable, self-reproducing cell population in normal epidermis.

Altered T cell subsets and function in polytransfused beta-thalassemia patients: correlation with sex and age at first transfusion.

Monoclonal antibodies (OKT series) have been used to investigate possible modifications of T lymphocytes and T lymphocyte subsets in 65 multiply transfused beta-thalassemia patients. No significant difference was observed in percentage and absolute number of OKT3-, OKT4-, and OKT8-positive cells when compared to controls. A subgroup of patients (10 patients, 15.3%), however, could be selected who showed a reversal of OKT4/OKT8 ratio. These patients did not differ from the others as to age, number of transfusions, frequency of splenectomy, ferritin levels, hepatitis B markers, chronic liver disease incidence, and numbers of B lymphocytes and natural killer cells. The features distinguishing this group from the remaining patients were: decreased mitogen responsiveness; early age when first transfused; high incidence of males (90%). Immunological investigation was done in 2 occasions, 1 year apart, but no significant modification was observed in these patients. These findings suggest that in beta-thalassemia patients transfusion therapy started very early in life may be responsible for persistent immunological modifications. The susceptibility to such modifications might be greater in males.

The effect of grenz rays on the expression of allergic contact dermatitis in man.

To investigate the effect of grenz rays on the expression of allergic contact dermatitis, six patients hypersensitive to nickel were studied. They were given 3 Gy of grenz rays, once a week for 3 weeks, to a defined area of the back. Twenty-four hours after the last treatment serial dilution nickel patch tests were applied on the grenz-ray-treated area and on untreated control skin. There was an almost total suppression of the allergic contact dermatitis at the site of grenz ray treatment. Biopsy specimens were taken from nickel-challenged and unchallenged skin, both from the grenz-ray-treated area and from the control area. Different cell populations in epidermis and dermis were identified by monoclonal antibodies (Leu 2, 3, 4, 7, Leu M1, B1, OKT6). In the grenz-ray treated epidermis there was a pronounced reduction of OKT6-positive cells, regarded as Langerhans cells. No other differences were observed between control and grenz-ray-treated skin. Our results suggest that Langerhans cells might be required also for the effector phase of the allergic contact dermatitis.

977 RECURRENT PANNICULITIS ASSOCIATED WITH CYTOTOXIC T LYMPHOCYTES

There is little understanding of the pathogenesis of recurrent panniculitis. It was therefore of interest to find a patient with widespread panniculitis characterized by a specific pattern of inflammatory lymphocytes in the lesions. The C-reactive protein (5.4 mg/dl) and serum immunoglobulins were elevated. Cultures of the lesions were sterile. Her indium-labelled blood leukocytes were found at the sites of subcutaneous lesions. Biopsies of the lesions revealed a lobular panniculitis characterized by many lymphocytes and macrophages but few other types of leukocytes. In addition, few lymphocytes or macrophages were found in the dermis. The types of lymphocytes in the lesions were examined by immunoperoxidase techniques. No immunoglobulin containing cells were found; virtually all lymphocytes were OKT3 positive. Furthermore, no OKT4 positive cells were found, whereas many OKT8 positive cells were identified. She was treated with oral prednisone because of the sensitivity of cytotoxic/suppressor I cells to corticosteroids. Following that treatment, the lesions desappeared promptly and repeat indium scan showed no leukocyte migration to the skin lesions. Furthermore, when the corticosteroid dose was reduced, the lesions rapidly reappeared and the immunohistopathology of those lesions was indistinguishable from the initial ones. Thus, it appears that the panniculitis in this case may be associated with an influx of cytotoxic T cells.

Disproportionate lymphoid cell subsets in thalassaemia major: the relative contributions of transfusion and splenectomy

The relative proportions of T-cell (OKT3-positive, OKT4-positive and OKT8-positive) and B-cell (SIg-positive) populations in peripheral blood obtained from 29 chronically transfused patients with beta-thalassaemia major were compared with those of 17 healthy controls. Changes attributable to blood transfusion and/or splenectomy are described. The percentage of OKT8-positive (T-suppressor) cells found in the thalassaemic patients increased linearly (P less than 0.001) with the number of units transfused, irrespective of splenectomy. The percentage of OKT4-positive (T-helper) cells varied inversely with increasing transfusion in nonsplenectomized patients while in those who were splenectomized no significant correlation was apparent. Thus, in both groups of patients the T4/T8 ratio declined in a transfusion-related manner. The splenectomized patients experienced a marked and persistent lymphocytosis due to an increase in the number of both T- and B-cells. When the results were expressed as percentages, the greatest increase occurred in the number of B-cells, this increase being unrelated to the number of transfusions received. None of the serum parameters usually associated with iron overload or abnormal liver function correlated with the observed increases in T-suppressor and SIg-positive cells. These findings corroborate reports that transfusion of blood products may lead to decreased T4/T8 ratios. However, none of the patients studied manifested clinical signs of acquired immune deficiency syndrome (AIDS). Accordingly, studies which define transfusion related AIDS on the basis of analyses with monoclonal antibodies must be viewed with caution.

Anti-lymphocyte antibodies in patients with the acquired immune deficiency syndrome

Human lymphotropic retroviruses lymphadenopathy-associated virus/human T lymphoma virus III have been recently implicated In the pathogenesis of the acquired immune deficiency syndrome (AIDS). The mechanisms leading to the complex immune deregulations of this disease, however, are still largely unknown. To investigate the possible presence of anti-lymphocyte antibodies, lymphocytes from a normal donor were incubated with serum samples from patients with AIDS. Substantial increases of up to 75 percent in the number of surface immunoglobulin-positive lymphocytes resulted from incubation with serum of patients with AIDS and AIDS-related complex but not with serum of patients with non-AIDS-related diseases or of normal control subjects. Monoclonal antibodies to OKT11, OKT4, and OKT8 in conjunction with a double-labeling technique were then used to identify the type of surface immunoglobulin-positive lymphocytes. These experiments showed that binding of immunoglobulins to lymphocytes did not occur at random but was directed against OKT4- or OKT11-positive cells whereas OKT8-positive cells showed no detectable reactivity. The results of these studies indicate that patients with AIDS and AIDS-related complex have circulating antibodies capable of reacting selectively with a population of T cells that is predominantly composed of helper cells and does not include suppressor cells. The augmentation of surface immunoglobulin-positive lymphocytes in the patients studied consistently paralleled the marked decreases of the helper/suppressor cell ratios and the presence of circulating anti-human T lymphoma virus III antibodies. Binding of antibodies to the surface of helper T cells may be a determining event in the pathogenesis of this disease.

T-cell subsets in the hyporesponsiveness to hepatitis B surface antigen (HBsAg) and antigen-specific suppressor lymphocytes in chronic hepatitis B virus (HBV) infection

In contrast to convalescent hepatitis B patients, who exhibit the ability to elicit a specific immune response to HBsAg, patients with chronic hepatitis B virus (HBV) infection are markedly hyporesponsive to HBsAg and show a decrease in the nomal ratio of OKT4-positive (helper/inducer) to OKT8-positive (suppressor/cytotoxic) lymphocytes. In this study the role of OKT4-positive and OKT8-positive cells on cellular immune response to HBsAg was evaluated in patients with chronic HBV infection and the ability of such patients to develop antigen-specific suppressor lymphocytes after in vitro sensitization of HBsAg. Elimination of OKT8-positive cells markedly improved the in vitro lymphocyte proliferative response to HBsAg without altering the reactivity of cells from the same donor to PPD or Candida. In contrast, the degree of responsiveness to HBsAg was not affected by the depletion of OKT4-positive cells. In vitro coculture experiments, performed in the seven chronically HBV-infected patients who showed a proliferative response when their PBM were cultured with purified HBsAg or PPD, have demonstrated that lymphocytes from chronic HBV carriers, stimulated with HBsAg, inhibit the response of autologous PBM to HBsAg but not to the unrelated antigen PPD.

Increased number of OKT6-positive dendritic cells in the hair follicles of patients with alopecia areata.

In 6 patients with untreated alopecia areata in the progressive stage, 6 in the stationary stage, and 6 normal individuals as controls, an in situ analysis of OKT6-positive dendritic cells in hair follicles, and peribulbar and intrabulbar infiltrates was performed using the avidin-biotin-peroxidase method with monoclonal antibodies. In controls, OKT6-positive dendritic cells were distributed only in the upper portions of hair follicles and were not observed in the bulbar area, and the percentage of these cells among all epithelial cells of the hair follicles was 1.0 +/- 0.1% (mean +/- SE). In stationary-stage patients, the distribution and the percentage of positive cells were the same as those for the controls (1.1 +/- 0.1%). In the progressive stage, however, positive cells were distributed in both the upper portions of the hair follicles and the bulbar area, and the percentage of positive cells (4.9 +/- 0.3%) was significantly higher than that of controls. Staining for T, B lymphocytes and T cell subsets in the peribulbar infiltrates revealed a predominance of OKT4-positive cells (the OKT4/OKT8 ratio was from 3:1 to 4:1). This indicates that the number of OKT6-positive dendritic cells increases in the hair follicles of progressive alopecia areata and that these cells may play an important role in cooperation with T cells in the pathogenesis of alopecia areata.

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)

こう原病患者に対する血しょう交換療法

Plasma exchange was performed in a total 18 patients of 11 rheumatoid arthritis (RA), 3 progressive systemic sclerosis (PSS), 1 polymyositis (PM), 1 dermatomyositis (DM) and 2 mixed connective tissue disease (MCTD) . Serum levels of immunoglobulins and complement and also numbers of lymphocyte subsets and its function were measure before and after treatment. Plasma separator AP-05-H (ASAHI Medical Co.) with menbrane filters was used as substitute for the exchanged plasma of 2, 000 to 3, 000ml in each trial.The treatment seemed to be effective in 9 of 11 RA patients and two of which showed a disappearance of their subcutaneous nodules. The Skin ulcers in the legs found in 2 PSS patients decreased in their size and sclerosis of the skin found in one PSS patient relieved. Respiratory disorder found in one PM patient improved. Muscle weakness and histologic finding of myositis found in one DM patient improved. Severe myalgia and muscle weakness in one MCTD patient improved.In laboratory data, serum levels of total protein, γ-globulin, immunoglobulin class of IgG, IgA and IgM, C3 and C4 decreased significantly. Decrease of numbers of OKT-8 positive cells and increase of the ratio of OKT-4/OKT-8 positive cell were significant.

Lymphocyte subsets in infants: relationships to feeding, atopy, atopic heredity and infections.

Numbers of T and B lymphocytes and T cell subsets were measured longitudinally in blood samples of 68 healthy infants from 1 month to 28 months of age. Monoclonal antibodies against cell surface antigens (OKT3, OKT4, OKT8, and OKIal) and antibodies to immunoglobulin heavy chains (gamma, mu, alpha and delta) were used for immunofluorescent staining. The absolute number of T lymphocytes (OKT3) was found to be highest at the age of 6-7 months, reflecting the greater numbers of both helper (OKT4) and suppressor (OKT8) cells. The percentages of OKT4 and OKT8 positive cells and hence the ratios of these cells were very stable throughout the study period. Relatively, breast-fed infants had more suppressor (OKT8) cells than infants on formula, but the difference was not apparent in absolute counts. Change to formula feeding caused an increase in B cells. The heredity for atopy did not influence the total numbers of T cells or cell numbers in the different subgroups. At the age of 4 months an altered helper/suppressor ratio was noted in infants who later developed a severe atopy. At the age of 28 months the relative number of T cells was lower in atopic than nonatopic infants. The rate of respiratory infections did not affect these numbers.

Altered T Cell Subsets and Function in Poly transfused β-Thalassemia Patients: Correlation with Sex and Age at First Transfusion

Monoclonal antibodies (OKT series) have been used to investigate possible modifications of T lymphocytes and T lymphocyte subsets in 65 multiply transfused β-thalassemia patients. No significant difference was observed in percentage and absolute number of OKT3-, OKT4-, and OKT8-positive cells when compared to controls. A subgroup of patients (10 patients, 15.3%), however, could be selected who showed a reversal of OKT4/OKT8 ratio. These patients did not differ from the others as to age, number of transfusions, frequency of splenectomy, ferritin levels, hepatitis B markers, chronic liver disease incidence, and numbers of B lymphocytes and natural killer cells. The features distinguishing this group from the remaining patients were: (1) decreased mitogen responsiveness; (2) early age when first transfused; (3) high incidence of males (90%). Immunological investigation was done in 2 occasions, 1 year apart, but no significant modification was observed in these patients. These findings suggest that in β-thalassemia patients transfusion therapy started very early in life may be responsible for persistent immunological modifications. The susceptibility to such modifications might be greater in males.

Current research on immunopathology of melanoma: analysis of lymphocyte populations in relation to antigen expression and histological features of melanoma

Immunoperoxidase localization of monoclonal antibodies in sections of melanoma has been used to identify histological features which may be of prognostic importance in melanoma, in particular whether certain structures on melanoma cells may determine the degree and nature of lymphoid infiltrates and whether these may be related to prognosis. Monoclonal antibodies to lymphocyte subpopulations were used to identify and quantitate lymphoid infiltrates in 15 primary melanomas and 8 cutaneous metastases. These were correlated with histological features identified in routine sections. There was a wide variation in the numbers of mononuclear cells associated with both primary and metastatic melanoma. T cells and to a lesser extent macrophages accounted for the majority of the cells, B cells and natural killer (NK) cells for only 2% of the infiltrates. The Leu 3a (helper) T cell subpopulation predominated in primary tumours, OKT8 positive (suppressor/cytotoxic) cells in metastases. Infiltrates in which OKT8 cells predominated were associated with ulceration, a high mitotic rate and thick primary tumours. The converse applied to Leu 3a infiltrates. Infiltrates with a high proportion of Leu 3a positive cells tended to be associated with Thy-1 positive, DR antigen negative tumours. Thy-1 antigens were predominantly expressed on primary tumours and rarely on metastases whereas the converse applied to expression of the acute lymphoblastic leukemia antigen (CALLA) on melanoma cells. These findings suggest that certain melanoma antigens may be related to the nature of the lymphoid infiltrate associated with melanoma and possibly with the behaviour of the tumour in the host. They further suggest that identification of cell surface structures and lymphoid infiltrates by these techniques may be a valuable extension of routine histopathological assessment of prognosis in melanoma.

Clinical and histological features of dry skin in atopic dermatitis.

Of 200 atopic dermatitis patients observed during cold months, 44 (22%) had ichthyosis vulgaris. Histologically, the dry skin in atopic dermatitis coexistent with ichthyosis demonstrated ichthyotic features which were frequently superimposed with eczematous changes. The dry skin in pure atopic dermatitis demonstrated the histology of mild eczema. Examinations using monoclonal antibodies showed that the dry skin in pure atopic dermatitis had increased numbers of OKT6-positive cells in epidermis. The lymphocytes in the dermal infiltrates consisted predominantly of LEU-3a-positive cells. It is concluded that the dry skin often seen in atopic dermatitis may be a mild eczematous lesion of atopic dermatitis, or a manifestation of concomitant ichthyosis, or a complex of these two changes.

Membrane phenotype and functional behaviour of T lymphocytes in hairy cell leukemia (HCL).

D ESPITE some controversy, hairy cell leukemia (HCL) is generally considered to be a chronic B cell lymphoproliferative disorder of the adult age,‘~d although some very rare cases with T cell features have also been described.5.6 Throughout the course of this disease, the major jeopardizing factor is the high risk of infective episodes,‘.* particularly after splenectomy, that nonetheless still remains the primary and most beneficial type of therapeutic intervention.‘.” Several other hypothesis have been put forward to account for the high incidence of these infections, including neutropenia and monocytopenia. Interestingly however, patients with HCL generally have normal levels of serum immunoglobulins”,‘2 unlike in other chronic B cell leukemias, namely chronic lymphocytic leukemia (B-CLL). ‘The recognition of the close interaction between T and B lymphocytes and in particular of the regulating function of T cell subsets in the maturation and differentiation of B cells into antibody-producing plasma cells” has shed further light on the possible role played by T cell defects in the B cell disorders. Among the different B cell chronic leukemias, B-CLL has been the most thoroughly studied, and both the phenotypic and functional abnormalities of the T cell population have been described. Indeed, an imbalance in the distribution of T lymphocyte subsets with an increase in the proportion of T cells expressing a suppressorcytotoxic phenotype (Ty, OKTS positive cells) together with a decrease in the proportion of the T cells with a helper-inducer phenotype (Tp, OKT4 positive cells) has been demonstrated,‘J-‘X particularly in patients with more advanced disease.” In addition, several T cells functional defects, like a decreased response to mitogens,20 a reduced T colony forming capacity,2’.22 a diminished helper activity in a pokeweed mitogen (PWM)-stimulated system,23.24 and a depressed natural killer (NK) activity25.2h have also been extensively documented. These observations strongly suggest that T cell abnormalities may be implicated in the clinical and laboratory features

Dipeptidyl peptidase IV as a new surface marker for a subpopulation of human T-lymphocytes

Plasma membranes were isolated from normal human lymphocytes as well as from cells of chronic lymphocytic leukemia of the T type. In both cases the bulk of the dipeptidyl peptidase IV activity paralleled the distribution of 5′-nucleosidase and, therefore, was localized in the plasmalemma. Immunofluorescence experiments with normal human lymphocytes and with antibodies against dipeptidyl peptidase IV revealed that this peptidase was accessible on the surface of viable cells. Further, it was demonstrated that the relative number of dipeptidyl peptidase IV-positive cells is much higher in lymphocytes reacting with the OKT4 antibody than in OKT8-positive cells. On the other hand, it has been reported that this peptidase is absent in B lymphocytes and is predominantly found in T cells bearing the Fc receptor for IgM (Tμ lymphocytes). Thus, it is concluded that dipeptidyl peptidase IV represents an easily demonstrable surface marker of this lymphocyte subset.

Defective regulation of immune responses in respiratory syncytial virus infection.

The relationship of suppressor cell numbers and function to virus-specific IgE response was determined in 72 infants with respiratory syncytial virus (RSV) infection. Monoclonal antibodies to membrane antigens were used to enumerate OKT4 and OKT8 antigen-positive cells, and suppressor cell function as quantitated by the degree of suppression of lymphocyte mitogenesis induced by incubation of lymphocyte cultures with histamine. Patients with bronchiolitis had fewer OKT8-positive cells during convalescence than patients with other forms of illness due to RSV (p less than 0.05). An inverse correlation of OKT8-positive cell numbers and peak IgE titers was observed (p less than 0.01). Histamine-induced suppression was also reduced in patients with bronchiolitis (p less than 0.05). In patients with repeated infection, improved histamine-induced suppression was associated with reduced virus-specific IgE titers and the absence of wheezing. Defects in immunoregulation may underlie previously recognized immunologic and pharmacologic abnormalities in patients with bronchiolitis.

Phorbol esters inhibit the functional activation of cytotoxic precursors in mixed lymphocyte cultures.

We have investigated the effect of phorbol esters on T cell activation and generation of suppressor and cytotoxic activity in mixed lymphocyte cultures (MLC). The presence of 30 nM P(Bu)2 during the sensitization phase inhibited the generation of allospecific cytotoxicity and also decreased the killing potential against NK-sensitive targets. The inhibition was not mediated by direct blocking of the lytic capacity nor by suppression of clonal expansion of cytotoxic cells through modulation of lymphokine production. The presence of P(Bu)2 enhanced cell proliferation, but inhibited the functional activation of lymphocytes and consequent generation of Dr antigen-positive T cells. Because the presence of the compound did not affect the MLC-induced generation of suppressor activity, it is likely that P(Bu)2 selectively blocks the maturation of cytotoxic precursors. Surface-marker analysis with OKT monoclonal antibodies revealed that the effects on lymphocyte activation were associated with a decrease in OKT3 and OKT4 reactivity and an increase in the percentage of OKT8-positive cells. The decrease in OKT4 reactivity was not due to selective loss of this lymphocyte subpopulation, because P(Bu)2 was equally mitogenic for the purified OKT4- and OKT8-positive subsets. The results suggest that the effect of P(Bu)2 on cell differentiation and its ability to modulate the expression of functional markers in lymphocyte subsets may interfere with T-T cell cooperation that controls the functional maturation of cytotoxic precursors.

Effect of a Thymic Factor on T Lymphocytes in B Cell Chronic Lymphocytic Leukemia: In Vitro and In Vivo Studies

Abnormalities of T lymphocytes in B cell chronic lymphocytic leukemia (B-CLL) have been extensively documented by several immunologic investigations. Following recent studies pointing to the favorable effect of TP-1, a partially purified extract of calf thymus, on the T cell-mediated immunity of several diseases, including Hodgkin's disease, we have used monoclonal antibodies and the enriched T lymphocytes of 16 untreated B-CLL patients to evaluate the proportion of T cell subsets before and after the administration of TP-1. In addition, the proliferative response to phytohemagglutinin (PHA) and the helper function in a pokeweed mitogen (PWM) system were assessed. In ten cases, the effect of TP-1 was also studied in vitro by evaluating the same parameters before and after incubation of B-CLL T cells with the drug. The study demonstrated that in vivo administration of TP-1 increases significantly (P less than .001) the proportion of the defective helper/inducer T cell population (OKT4-positive cells) in B-CLL, leading to a near normal OKT4/OKT8 ratio. Furthermore, the improved phenotypic profile was accompanied by an increased proliferative response to PHA and, in particular, by a significant increase (P less than .01) of T helper capacity; this increase was, however, insufficient to enable the normalization of the serum immunoglobulin levels. The in vitro incubation of B-CLL T lymphocytes did not succeed in producing significant modifications in distribution and function.