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PubMed1985

Human peripheral blood null lymphocytes stimulated by Staphylococcus aureus Cowan I produce atypical acid-labile interferon in vitro.

Peripheral blood mononuclear leucocytes (PBLs) stimulated in vitro by heat-killed formaldehyde-fixed Staphylococcus aureus Cowan I (SACoI) produced acid-labile alpha interferon (IFN-alpha) and, to various extents, also IFN-gamma. The IFN producers resided in nylon wool-nonadherent cells, and monocytes suppressed SACoI-induced IFN responses. Further separation of nonadherent PBLs in accordance with expression of surface antigenic markers was performed with a 'panning' technique. The SACoI induced production of IFN in cells that carried neither surface immunoglobulins nor OKT3-defined antigens. These cells were also characterized as OKM1- and OKT10-negative. In contrast, cells with natural killer (NK) activity against K562 erythroleukaemia cells were located in both OKM1- and OKT10-positive and -negative cells. At centrifugation on Percoll density gradients, cells with NK activity and IFN response against SACoI were recovered from light gradient fractions that contained mainly large granular lymphocytes (LGL). Furthermore, the IFN producers were enriched by removal of sheep erythrocyte-rosetting T cells from the Percoll fractions. These SACoI-induced IFN-producing PBLs are LGL but lack certain antigens that are frequently found on NK cells.

Antibodies, Monoclonal↗
PubMed1990

A distinct population of nonphagocytic and low level CD4+ null lymphocytes produce IFN-alpha after stimulation by herpes simplex virus-infected cells.

Human PBMC were stimulated for 6 h in vitro by HSV or Sendai virus (SV) and analyzed by flow cytometry. IFN-alpha producing cells (IPC) were identified through their content of IFN-alpha mRNA by in situ hybridization using a 35S-labeled IFN-alpha 2 cRNA probe. The IPC induced by HSV-infected WISH cells lacked capacity to adhere to and phagocytose latex particles. The induction of IFN-alpha by free infectious SV occurring in monocytes was abolished by phagocytosis of latex particles present in the cultures during the induction period. Such latex particles actually enhanced the IFN-alpha response induced by glutaraldehyde-fixed HSV- or SV-infected WISH cells or by free intact HSV. The HSV-induced IPC did not express the CD14 Ag expressed on monocytes. Cell sorting was performed on HSV-induced PBMC labeled with phycoerythrin-conjugated anti-CD3 and FITC-conjugated anti-CD4 mAb. A small population consisting of 1.4% of all PBMC, which was CD3- but expressed low but significant levels of CD4, contained the majority of the IPC with a 50-fold increase of their frequency. This cell population had a forward- and right-angle light scatter different from typical monocytes/macrophages. The results therefore further delineate IPC among PBMC into monocytes, being stimulated by viruses such as SV. Another distinct population of infrequent but highly efficient IPC, tentatively designated natural IFN-alpha producing cells, is activated by stimuli such as HSV.

Antibodies, Monoclonal↗
PubMed1979

Loss of circulating T lymphocytes with normal levels of B and 'null' lymphocytes in Thai adults with malaria.

Peripheral blood mononuclear cells from forty-nine Thai adults infected with either Plasmodium falciparum or Plasmodium vivax were examined in order to determine the percentage of T, B, and Fc-receptor-bearing cells present. In comparison to healthy controls, both the percentage and concentration of peripheral T cells were decreased in the malaria-infected individuals as assessed by formation of rosettes with sheep red blood cells. The percentage of peripheral B cells was increased but their concentration was unchanged, as assessed by two techniques: the presence of surface immunoglobulin and the presence of a complement receptor. Both the percentage and concentration of lymphocytes bearing Fc receptors were unchanged in infected individuals. Finally, calculation of the changes in 'null' cells (defined either as non-T, non-B lymphocytes or as non-T, non-B, non Fc-receptor-bearing lymphocytes) revealed an increase in the 'null' cell percentage but a decrease in the absolute number of 'null' cells. These data indicate that in adult Thai patients naturally infected with malaria, there is a real loss of circulating T lymphocytes with no real change in B, Fc-receptor-bearing, or 'null' lymphocytes.

Adolescent↗
PubMed1982

Parallel tubular structures in T,B and null lymphocyte subpopulations.

T, B and Null lymphocyte-enriched subpopulations were isolated by means of sheep red blood cell (E SRBC) sedimentation and nylon wool adherence. In these subsets the proportion of Fc receptor-bearing cells was determined by the antibody-coated human and ox erythrocyte rosette assays (EA Hu and Ox). In the T-cell fraction the proportion of Fc-bearing lymphocytes was dependent on the procedure by which the sheep erythrocytes were removed from the E SRBC rosette-forming cells. Mechanical vibration resulted in considerably higher percentages of EA rosette-forming cells (EA-RFC) than osmotic shock or lysis with ammonium chloride. In all three procedures the number of EA Hu-RFC was slightly higher than the number of EA Ox-RFC. In the B-cell fraction the proportion of EA Ox-RFC was higher than that of EA Hu-RFC, mean values 43 and 33%, respectively. In the Null cell fraction the reversed was seen: mean values 54% EA Hu-RFC and 45% EA Ox-RFC. In all three lymphocyte fractions the majority of the EA-RFC contained parallel tubular structures and/or associated amorphous granules. Non-Fc receptor-bearing lymphocytes only occasionally showed parallel tubular structures or the amorphous granules.

Animals↗
PubMed1977

Human peripheral blood "null-lymphocytes", a highly enriched pool for granulocytic stem cells (CFU-C).

A "Null"-lymphocyte preparation containing a high concentration of granulocytic stem cells (CFU-C) was isolated from human peripheral blood. 3 lymphocyte purification procedures were shown to produce an enrichment of CFU-C: 1. Removal of mononuclear phagocytes by iron phagocytosis and plastic adherence procedures. 2. Passage through Ig anti-Ig columns. 3. Removal of E-rosette-forming T cells. A combination of all 3 purification steps resulted in a 30- to 40-fold enrichment of CFU-C in the final "Null"-lymphocyte population as compared to the initial lymphocyte fraction isolated by Ficoll-Urografin density gradient centrifugation.

Animals↗
PubMed1980

Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. II. A hybridoma secreting antibody against an antigen expressed by human B and null lymphocytes.

A hybridoma (FMC4) has been derived which secretes antibody showing selective reaction with human B lymphocytes, monocytes and some null lymphocytes. Few, if any, T lymphocytes in normal blood are stained, although stimulation of lymphocytes with PHA leads to an increase in the proportion of cells reacting with the hybridoma antibody. The antibody reacts with B and null lymphoblastoid cell lines but not with T cell lines. B chronic lymphocytic leukaemia (CLL) cells but not T-CLLs are stained and null-type acute lymphoblastic leukaemia (ALL) cells but not T-type ALL also react. Normal blood myeloid cells do not react with FMC4 supernatant whilst some myeloid leukaemias do. The expression of the antigen reacting with FMC4 supernatant suggests that FMC4 may secrete an antibody against the human equivalent of the Ia antigen.

Antibodies↗
PubMed1977

Studies of T, B, and null lymphocytes during the course of acute lymphocytic leukemia.

The distribution of T, B and null lymphocytes was studied in the peripheral blood (PB) of 34 children with acute lymphocytic leukemia (ALL), at diagnosis and during the course of their disease. All patients received the same chemotherapy. At diagnosis, the proportion and absolute numbers of T lymphocytes fell into 2 groups, a "low" group (medians 8%, 318/mm3) and a "normal" group (medians 60%, 1405/mm3). Patients with a low proportion of T cells tended to have a high proportion and absolute number of null cells (correl. coeff. r = 0.94). This group has had high white blood cell counts (median = 29,600/mm3) and a high proportion of blasts (84%). During remission, the proportion of T cells returned toward normal (40-75%) in both groups. Four patients in the low T group relapsed; T cells again fell to low levels and returned to normal in response to new therapy. Three interpretations of these observations are suggested: 1) Active leukemia may cause normal lymphocytes (T cells and to a lesser degree B cells) to lose their surface markers; 2) Acute leukemia may inhibit maturation of normal lymphoid cells, and thus T or B markers are not sufficiently developed to be detectable; and 3) Cells without surface markers (null cells) may be a part of the malignant population, even though they are not morphologic blasts. Further studies are necessary to test these hypotheses.

Adolescent↗
PubMed1980

Alteration of T and null lymphocyte frequencies in the peripheral blood of human opiate addicts: in vivo evidence for opiate receptor sites on T lymphocytes.

Street opiate addiction produces a significant depression in the absolute number of total T lymphocytes in peripheral blood as measured by the ability of the lymphocytes to rosette sheep red blood cells (SRBC). Associated with the decrease in T cells, there is an increase in the absolute number of null lymphocytes but no significant changes in B lymphocytes or total white blood cell count. The T cell values for 2 different populations of addicts (n = 12 and 32) are 31.8% and 23.1%, whereas the null cell values are 51.1% and 57.6%, respectively. The values for comparable control populations (n = 18 and 10) are: T% = 70.7% and 67.4%, and null % = 9.2% and 14.5%. Self-reported use of marihuana does not significantly alter the distribution of cell populations. A 1- to 3-hr incubation of addicted-derived lymphocytes with 10(-6) to 10(-7) M Naloxone reverses both T cell depression and null cell increase by allowing the null cells to express SRBC receptors. Cyclic AMP and dibutyryl cyclic AMP can also convert the null cells to T cells. The conversion of null to T lymphocytes has additionally been measured by monitoring the increase in PHA-stimulated growth in 72-hr cultures as determined by tritiated thymidine incorporation into DNA. These results support the hypothesis that opiates can alter T lymphocyte number and function in vivo, and that this alteration may produce a significant degeneration in the immune competence of street opiate addicts.

B-Lymphocytes↗
PubMed1985

Elevated adenosine deaminase and purine nucleoside phosphorylase activity in peripheral blood null lymphocytes from patients with acquired immune deficiency syndrome.

The purine metabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are important in lymphocyte differentiation, and genetic deficiencies of either enzyme have been associated with hereditary immunodeficiency states. Both ADA and PNP activity were measured in null cell-enriched and T cell-enriched peripheral blood lymphocytes from 16 patients with the acquired immune deficiency syndrome (AIDS), seven patients with the AIDS-related symptom complex (ARC), and seven asymptomatic homosexuals. ADA activity in nmol/10(6) lymphocytes/h was significantly elevated in null lymphocytes from AIDS (161 +/- 12) as compared with 23 healthy heterosexual controls (127 +/- 8;P less than .025). PNP activity was also significantly increased in null lymphocytes from AIDS patients (96 +/- 10;P less than .005) as well as those from ARC patients (84 +/- 11:P less than .025) relative to controls (61 +/- 5). No significant differences in enzyme activity were noted in T cell-enriched cells in any group. Along with elevated enzyme activity, AIDS patients had small yet significant increases in the percentages of HLA-DR (P less than .025), terminal deoxynucleotidyl transferase (TdT) (P less than .0001), and peanut agglutinin receptor (P less than .0001) positive lymphocytes in the null fraction compared with controls. TdT-positive cells appeared morphologically as large lymphoblasts with irregular nuclei. The data imply that the cellular immune deficiency in AIDS is not a result of deficiencies in lymphocyte ADA or PNP activity, but is more likely associated with an increase in an immature and/or activated lymphocyte subset.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Natural killer lymphocytes: "null cells" no more.

Natural Killer (NK) lymphocytes were initially described as potent effector cells that, unlike T lymphocytes, were able to kill targets in the absence of a priori stimulation and without specific recognition mechanisms. Over the past ten years however, it has been clearly demonstrated that NK cell function is regulated by a number of surface receptors that bind specific ligands expressed by target cells. Some of these receptors display inhibitory functions and recognize MHC class I molecules expressed by normal autologous cells that, as a consequence, are spared from indiscriminate NK-mediated killing. Other receptors are involved in NK cell activation against allogeneic cells or cells that, upon viral infection or tumor transformation, down-regulate MHC Class I expression. Altogether these data provide important advances toward the understanding of the complexity of the molecular mechanisms that regulate NK-mediated functions.

Cytotoxicity, Immunologic↗
PubMed1985

Cells and mediators which participate in immunoglobulin synthesis by human mononuclear cells. I. The obligatory requirement of null lymphocytes in the synthesis of immunoglobulins in vitro.

The circulating mononuclear cells of normal adult human volunteers were fractionated into T and non-T lymphocytes. The T cells were then fractionated into TM and non-TM cells and the non-T cells were further fractionated, by both positive and negative isolation, into B cells and null cells. Culture of non-T cells, TM cells, and PWM for 7 to 8 days resulted in cytoplasmic Ig (cIg) synthesis by all B cells, as detected by immunofluorescence. However, culture of either purified B or null cells with TM cells and PWM resulted in a marked reduction (75%) of cIg-synthesizing cells. The addition of monocytes did not enhance cIg synthesis. Culture of reconstituted B and null cells with TM cells and PWM restored the capacity to synthesize cIg to the cells. It is concluded that null cells are required, as well as TM cells and PWM, for cIg synthesis by B cells.

B-Lymphocytes↗
PubMed1976

B, T and null lymphocytes in newborn infants and their mothers.

Estimation of B, T and null cells were performed on 29 newborn healthy babies and 16 mothers. The lymphocytes were isolated from peripheral venous blood, which is considered to be more representative of the immune state in the newborn than the cord blood. B lymphocytes were estimated by cytofluorometric measurements, T lymphocytes by sheep red blood cell rosette technique, (SRBC-R). Combined immunofluorescence and SRBC-R technique revealed the null cells. In the newborn babies the amount of B and T cells were found to be diminished. In the mothers the amount of B lymphocytes were low compared with normal adults. The rather high null cell percentage found in the babies might represent immature precursor cells. Mothers seem to be immuno-depressed as reflected in the low amount of B cells.

Adult↗
PubMed1986

Accumulation of immature B and null lymphocytes in the periphery after intraperitoneal administration of traditional Chinese medicine, xiao-chai-hu-tang (Japanese name: shosaiko-to).

Accumulation of lymphocytes after an intraperitoneal (ip) injection of a traditional Chinese herb medicine, XIAO-CHAI-HU-TANG (Japanese name: shosaiko-to), was investigated. Shosaiko-to induced marked accumulation of lymphocytes rather than macrophages in the peritoneal cavity of ICR mice, whereas various kinds of irritants, e.g. proteose-pepton, Escherichia coli lipopolysaccharide (LPS), OK-432 and Corynebacterium parvum, induced preferential accumulation of macrophages rather than lymphocytes. By means of analysis using two-color fluorescence-activated cell sorter (FACS), it was revealed that the increased lymphocyte subpopulations not only in the peritoneal cavity but also in the spleen of C3H/He mice by the injection of shosaiko-to were comprised of both immature B (IgM+ and IgD-) and null (thyl- and Ig-) cells. This effect of shosaiko-to was observed in other C5 normal strains, C3H/HeJ (LPS-nonresponder), C57BL/6, BALB/c and athymic nu/nu (ICR background) mice, but not in C5 deficient strains, AKR/J, A/J and DBA/2 mice, indicating that the accumulation of immature B and null cells in the periphery induced by shosaiko-to is closely related to the complement system.

Animals↗
PubMed1978

Characterization of a unique cell line (LAZ 221) from human acute lymphocytic ("null" cell) leukemia.

A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the "null" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines.

Adult↗
PubMed1980

Sensitivity of leukemic human null lymphocytes to deoxynucleosides.

The growth of cultured leukemic T-lymphocytes is readily inhibited by deoxynucleosides, particularly thymidine, deoxyguanosine, and deoxyadenosine. By contrast, Epstein-Barr virus-transformed B-lymphocytes are relatively resistant to deoxynucleosides. Growth inhibition correlates with the development of high deoxyribonucleoside triphosphate pools following exposure to deoxynucleosides. Leukemic T-lymphocytes are deficient in ecto-5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) activity, and it has been postulated that deficiency of this enzyme decreases the capacity of these cells to degrade deoxyribonucleotides, rendering them sensitive to deoxynucleosides. We find that the sensitivity of cultured null-type leukemic lymphocytes to growth inhibition of deoxynucleosides is similar to that of T-cells. However, the null cells contain normal levels of ecto-5'-nucleotidase. We infer that ecto-5'-nucleotidase deficiency does not have a central role in determining the deoxynucleoside sensitivity of leukemic lymphocytes.

B-Lymphocytes↗