G. Gasparotto

T-lymphocyte subpopulations in chronic lymphocytic leukemia: A quantitative and functional study

In the peripheral blood of patients with chronic B‐cell lymphocytic leukemia (B‐CLL) absolute numbers of E‐rosetting lymphocytes were increased. The proportions of TG and TM cell subsets were analyzed, as were their effects on the pokeweed mitogen (PWM)‐dependent differentiation of normal allogenic B cells or of autologous leukemic cells. The TG lymphocyte subset was further studied for its cytotoxic activity in antibody‐dependent cellular cytotoxicity (ADCC). A marked increase both in percentages and in absolute numbers of TG cells was found. TM lymphocytes percentages were normal, but because of the T lymphocytosis occurring in all patients, the absolute numbers of TM were increased. TM and TG subsets showed helper and suppressor activity, respectively, in PWM‐induced B‐cell differentiation. TG cells displayed effector cell activity in ADCC. The results provide further evidence that T lymphocytes from patients with B‐CLL are functionally normal. However, a noticeable increase of the T‐cell subset having suppressor and cytotoxic activity in ADCC was observed. This may be the consequence of a normal immune reaction to the leukemic population.

Immunoregulation in sarcoidosis.

Abstract The immunoregulatory function of lymphocyte subpopulations was studied in 38 sarcoidosis patients subdivided according to their clinical stage and disease phase. Functions studied included the percentage and absolute numbers of TG and TM lymphocytes and their ability to help and suppress the PWM-induced B-cell differentiation of normal allogenic and autologous B cells. The percentage of TG cells was increased in both active and inactive sarcoidosis, whereas their absolute number was increased only in the active phase of disease. This increase in TG cells was unaffected by pronase treatment and the Fc-IgG receptors were modulated as well as normal TG lymphocytes. The percentage of TM cells appeared statistically reduced only in active sarcoidosis while their absolute number, considering the lymphopenia, appears uniformly reduced in both phases of the disease. Functional analysis in the PWM-induced plasma cell generation assay revealed that TG sarcoid lymphocytes retain the property of suppressing B-cell differentiation, suggesting a quantitative imbalance without qualitative alterations. Aside from being diminished, the TM cells were not able to provide an optimal intracytoplasmic Ig production thereby supporting the presence of a qualitative deficiency. B sarcoid cells when cocultured with autologous Tnon-G populations in the presence of a polyclonal activator showed an impairment in plasma cell production; however, B-cell function was almost completely restored when the help was provided by normal Tnon-G lymphocytes, suggesting that the abnormalities observed in sarcoid patients are entirely related to alterations in the T immunoregulatory functions. The implications of the finding of increased suppressor and diminished helper activity in sarcoidosis patients are discussed.

Active and late rosette-forming cells: Immunological and cytochemical characterization

Abstract In order to characterize T-cell subpopulations with different affinities for sheep red blood cells, a possible correlation between active and late rosette-forming cells (RFC), expression of Fc receptors, and the presence of Ia antigens was investigated. Further analysis of their spontaneous in vitro DNA synthesis, and their cytochemical pattern was also performed. Most of the active T cells lacked Fc receptors and expressed Ia antigens, whereas the large majority of cells with Fc-IgG and -IgM receptors were included as late T cells, but lacked Ia determinants. Analysis of spontaneous blastogenesis showed that late RFC, but not active RFC, synthesize DNA in unstimulated cultures. Cytochemical analysis suggested that Active RFC display a more immature phenotype compared to late RFC, which have enzymatic markers present in mature T cells. Possible interpretations of these findings are discussed.

Immunobiology of Primary CNS Tumors in Infancy and Childhood

The authors report their experience on the immunological monitoring of children with posterior fossa medulloblastomas. The most important findings concerning humoral and cell-mediated immunity in this kind of patient are discussed. Among the main immunobiological pictures, the authors stress the remarkable failure of the T-cell dependent immune response, generally correlated to the degree of malignancy of the tumor, and the characteristic appearance of cells with natural cytotoxic activity, whose precise outlining is, at present, in progress. The B-cell dependent pool, mostly investigated through immunofluorescence studies, turned out to be very close to normal.

D cells with cytotoxic activity in acute lymphoblastic leukemia

Abstract Peripheral blood T lymphocytes bearing receptors for complement (D cells) from a patient with acute lymphoblastic leukemia were studied. Surface markers, in vitro functional characteristics, and cytochemical stains confirmed the thymic origin of these cells and an early stage of cellular differentiation. The finding of increased cellular cytotoxicity (mostly antibody dependent) was of notable interest. This study supports the hypothesis that D cells are cytotoxic lymphocytes.

Active E rosette-forming cells in the peripheral blood of cancer patients

Abstract The percentage and the absolute number of cells forming active and total E rosettes were determined in 107 patients with tumors of the lung or esophagus or glioblastomas. Although both the active and total E rosette forming cell subpopulations of T lymphocytes were decreased in cancer patients, the percentage of reduction of the active rosettes was more pronounced and paralleled the depression of other parameters of T-dependent immunity. Therefore, evaluation of the active T cell subpopulation may provide a rapid and useful test in monitoring the immune function of patients affected with neoplasias.

Über den möglichen Einfluß plasmatischer Faktoren auf die lymphozytäre Stimulierbarkeit und E-Rosetten-Bildung bei primär chronischer Polyarthritis

SummaryThe lymphocytes blastigenesis to PHA in culture with autologous or normal plasma, the formation of E rosettes and the presence of immunoglobulins on the lymphocytes surface were evaluated in 51 patients with chronic primary polyarthritis. While the percentage of T and B cells was almost normal (52.1±2.1% and 18.1±1.1%, N.V. 55.6±2.0% and 16.2±0.8%), the blastigenesis was significantly reduced in cultures with a 25% autologous plasma (5399±709 cpm compared to 13,182±920 cpm of the normal standard) and returned towards normal values when it was replaced by the plasma of a normal subject (12,189±1 081 cpm). The rheumatoid plasma was capable of reducing the blastigenesis in 11 normal subjects (7 395±750 cpm). The preincubation for 90′ of the lymphocytes of 14 controls in rheumatoid or autologous plasma induced a significant reduction in the formation of spontaneous rosettes (40.8±1.4% and 56.2±1.7%). These results suggest that the reduced function of the T lymphocytes in this disease is due to plasma factors.ZusammenfassungEs wurde in vitro an 51 Patienten mit chronischer Polyarthritis die lymphozytäre Blastogenese zu PHA in Kulturen mit autologem oder normalem Plasma sowie auch die E-Rosetten-Bildung und die Gegenwart an Oberflächen-Ig untersucht. Während der Prozentsatz an T- und B-Zellen fast normal bleibt (52,1±2,1% und 18,1±2,1%, n.W. 55,6±2,0% und 16,2±0,8%), ist die Blastogenese in den Kulturen mit 25% autologem Plasma (5 399±709 cpm gegen dem Standartwert von 13 182±920 cpm) bedeutend verringert. Diese kehrt fast zu den Normalwerten zurück, sobald man das Patientenplasma mit Plasma von Gesunden ersetzt (12 189±1 081 cpm). Das rheumatoide Plasma ist imstande die Blastogenese von 11 normalen Personen zu hemmen (7 395±750 cpm). Eine vorhergehende Inkubation für 90′ der Lymphozyten von 14 Kontrollpersonen in rheumatoidem oder autologem Plasma führt zu einer bedeutenden Differenz in der E-Rosettenbildung (40,8±1,4% und 56,2±2,1%). Dies bedeutet das die funktionelle Hemmung der T-Lymphozyten bei dieser Krankheit auf plasmatische Faktoren zurückzuführen ist.

Mitogenic action of neuraminidase

A new effect of NCV on lymphocytes is demonstrated. This property is the capacity to act as a mitogen in and of itself. The possible mechanisms of this phenomenon are discussed.

Shedding and resynthesis of receptor for mouse red blood cells on lymphocytes from healthy subjects and chronic lymphatic leukaemia patients

Abstract The shedding and resynthesis of receptors binding mouse red blood cells was investigated in lymphocytes of normal peripheral blood and in that of chronic lymphatic leukaemia patients. In the first hours after incubation the release of the receptor from the membrane is observed and its resynthesis occurs after 5 h. Metabolic poisons inhibit the reappearance of receptor while specific inhibitors for protein synthesis do not influence these phenomena. Compared with normal lymphocytes, cells from CLL patients show different patterns of shedding and resynthesis of receptors suggesting an altered metabolism of leukaemic lymphocytes.