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T Abo

Publications and source records attributed to T Abo.

At least 235 records · Page 13Linked to original sources

Suppressor cell function of human granular lymphocytes identified by the HNK-1 (Leu 7) monoclonal antibody.

The HNK-1 (Leu 7) differentiation antigen defines a subpopulation of human granular lymphocytes with natural killer (NK) and K cell function. In this study, we investigated whether HNK-1+ cells, identified with the monoclonal antibody and purified with a fluorescence-activated cell sorter (FACS), could function as suppressor cells. The results demonstrated that purified HNK-1+ cells efficiently suppressed both PWM-induced IgG production by B cells and T cell proliferation in mixed lymphocyte reactions (MLR). Manifestation of this suppressor cell activity required immune complex activation and was partially sensitive to 2000 rad irradiation. This suppressor cell activity was predominantly mediated by a subset of HNK-1+ cells that have previously been shown to have maximum NK function and lack expression of the E rosette (ER) receptor and T cell antigens (e.g., T3 and T8). Thus, HNK-1+ER- cells suppressed a MLR by an average 52%; HNK-1+ER+ were one-half as efficient, causing an average 23% suppression. For comparison, we also examined the characteristics of Leu 2a+ suppressor T lymphocytes. In contrast to HNK-1+ cells, unactivated Leu 2a+ cells suppressed both B and T cell responses. This suppressor activity was not augmented by immune complex activation and was absolutely radio-sensitive in PWM assays. HNK-1+ cells, especially the HNK+ER- subset, can therefore mediate suppressor cell function in addition to their spontaneous cytotoxic function. Furthermore, some of their suppressor cell properties are distinct from those attributed to other types of suppressor lymphocytes.

Antibodies, Monoclonal↗

Usefulness of monoclonal antibodies in the diagnosis and monitoring of patients with primary immunodeficiencies: combined experience in three clinical immunology centers.

Circulating levels of T-cell subsets and NK cells were determined in 78 patients with primary immunodeficiencies, 35 children with recurrent respiratory infections, and healthy age-matched controls. Normal T cell and natural killer (NK) cell values were observed in individuals with immunoglobulin A (IgA) deficiency and X-linked agammaglobulinemia, while reduced OKT4/OKT8 cell ratios and low levels of 5/9+ T helper cells were found in approximately 60% of patients with common variable immunodeficiency. Infants with severe combined immunodeficiency (SCID) and lymphopenia had virtually no cells expressing T-cell or NK-cell surface antigens, but had normal numbers of monocytes and other types of blood cells. Infants with DiGeorge syndrome, other primary T-cell defects, or SCID with B cells had few or no circulating cells of mature T helper-suppressor phenotypes, but had normal numbers of NK cells (HNK-1+) and NK function. These results support the idea of a common stem cell precursor for T, B, and NK cells, each of which follows a separate pathway of differentiation. Profound alterations were observed in the distribution and function of T-cell subsets in ataxia-telangiectasia patients who were previously shown to have thymic dysplasia. A significant reduction in the frequencies of OKT3+ and OKT4+ cells was observed in children with frequent respiratory infections during infancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Agammaglobulinemia↗

Interleukin 2 receptor expression by activated HNK-1+ granular lymphocytes: a requirement for their proliferation.

A subpopulation of HNK-1+ cells was found to express interleukin 2 receptor (IL 2R) as monitored by the anti-Tac monoclonal antibody after lectin or allogeneic cell stimulation. When blood mononuclear cells were stimulated with phytohemagglutinin (PHA) or concanavalin A for 3 days, or with pokeweed mitogen or allogeneic mononuclear cells for 6 days, virtually all of the HNK-1+ cells remained as small resting lymphocytes. One-fourth of these HNK-1+ cells expressed IL 2R, however, usually within 18 hr after stimulation. Neither circulating HNK-1+ cells nor unstimulated HNK-1+ cells in short-term culture expressed IL 2R. Only the subset of HNK-1+ cells that expressed T cell surface markers, such as the sheep erythrocyte receptor and Leu-4 antigen, could be induced to express IL 2R. When long-term cultures of HNK-1+ cells were established with initial PHA stimulation and the continued presence of IL 2, a majority of the cells was found to express the IL 2R. When anti-Tac antibody was added to the long-term cultures, proliferation of the HNK-1+ cells was completely inhibited. These results suggest that entry into growth cycle by this subpopulation of HNK-1+ granular lymphocytes may require two signals: a relatively nonspecific ligand interaction with cell surface glycoprotein(s) to induce expression of IL 2R, and subsequent IL 2 interaction with these specific cell surface receptors.

Adult↗

HNK-1 monoclonal antibody (Leu-7) in the identification of abnormal expansions of large granular lymphocytes.

Among 12 cases of chronic T lymphoproliferative disorders we observed, six patients showed an expansion of mononuclear cells with azurophilic granules usually referred to as large granular lymphocytes or LGL. Cells obtained from five patients with these abnormal LGL proliferations were studied with several surface markers including their reactivity with the HNK-1 monoclonal antibody reported to be specific for LGL. Cells in four out of five cases were HNK-1 positive. Whereas normal LGL have been reported to be unreactive with several T cell markers, three cases showed the co-existence of HNK-1 and surface markers expressed by T cells. Two cases were characterized by the proliferation of OKT8 cells. Cells from one patient were HNK-1 positive but did not express T or monocytic antigens. These cells were apparently not completely mature since alpha-naphthyl acetate acid esterase activity was negative. Cells from the remaining case were HNK-1 negative and positive for T and monocytic antigens. An increase of OKT-10 cells was observed in only one patient. Our data indicate that proliferations of LGL represent a remarkable proportion of the rare cases of sheep erythrocyte rosetting chronic lymphocytic leukaemias or lymphomas. Besides the morphology of LGL, the rosetting ability and the negativity for peroxidase, cells from these cases showed a vast heterogeneity of other structural and functional markers, possibly reflecting different stages in the maturation of these cells. The HNK-1 monoclonal antibody proved to be an important marker in the identification of these cases.

Adult↗

Postnatal expansion of the natural killer and keller cell population in humans identified by the monoclonal HNK-1 antibody.

Human natural killer (NK) and killer (K) cells were directly enumerated using a monoclonal antibody (HNK-1) and an immunofluorescence assay. The frequency of cells bearing surface HNK-1 antigen was very low in the newborn (less than 1.0%) and increased progressively through childhood and into adult life. This was correlated with an age-related increase in functional NK and K cell activities. Males had a slightly higher proportion of HNK-1+ cells than females. In addition to HNK-1 expression on the surface membrane, a prominent cytoplasmic expression of HNK-1 antigen was found in some but not all surface HNK-1+ cells. The cytoplasmic accumulation of HNK-1 molecules appeared to occur in more mature cells of this lineage.

Adolescent↗

Natural killer (HNK-1+) cells in Chediak-Higashi patients are present in normal numbers but are abnormal in function and morphology.

Children with the Chediak-Higashi (CH) syndrome are known to have abnormalities of natural killer (NK) cell function. We used the HNK-1 monoclonal antibody that reacts specifically with human NK and K cells to distinguish whether this abnormality was due either to a numerical deficiency of NK cells or a defect in their ability to function. In eight CH patients, a significant proportion of their blood mononuclear cells (10--19%) expressed the HNK-1 differentiation antigen. The level of NK cells in the five children with CH syndrome was higher than for age-matched normal controls (15.8% vs. 5.8%, P less than 0.001). When HNK-1+ cells were isolated with a fluorescence-activated cell sorter, the NK cells from CH patients were a homogeneous population of lymphocytes with a single large granule rather than the multiple small granules seen in Nk cells from normal individuals. The purified HNK-1+ cells from the CH patients had minimal NK or K cell function. The CH syndrome thus includes a functionally defective population of NK cells that retain the capability of expressing the HNK-1 differentiation antigen.

Adolescent↗

Characterization of HNK-1+ (Leu-7) human lymphocytes. I. Two distinct phenotypes of human NK cells with different cytotoxic capability.

Human lymphocytes with NK and K cell activities can be identified by the HNK-1 (Leu-7) monoclonal antibody. In these experiments, subsets of HNK-1+ cells from blood and bone marrow were distinguished by their expression of other cell surface antigens, their morphology, and their NK functional capability. Two-color immunofluorescence analysis revealed that subpopulations of HNK-1+ cells in blood expressed antigens found on mature T cells (e.g., T1, T3, T4, T8), but none expressed antigens characteristic of immature T cells (T6, T9). The majority of HNK-1+ cells (greater than 60%) also expressed a myeloid antigen (M1), whereas a minority (less than 25%) expressed HLA-DR. HNK-1+ cells were separated into T3- and T3+ subsets with the fluorescence-activated cell sorter and analyzed for their morphology and NK cell function. HNK+T3- cells exhibited a high level of NK activity against K562 target cells and contained many cytoplasmic granules. On the other hand, HNK+T3+ cells had low NK activity and a paucity of cytoplasmic granules. The cell sizes of HNK+T3- and HNK+T3+ cells were indistinguishable by light-scatter analysis. When these cell fractions were analyzed further, a reciprocal relationship between T3 and M1 antigen expression was observed. These results thus delineate two distinct subsets of human HNK-1+ cells in blood with different cytotoxic capability: HNK+T3-M1+ and HNK+T3+M1- cells. Analysis of bone marrow cells demonstrated that only 0.7% of the nucleated cells expressed the HNK-1 antigen; virtually all of these cells expressed both the T3 and T8 antigens but lacked the M1 antigen. Thus, a majority of HNK-1+ cell population in blood were T3-M1+, whereas almost all bone marrow HNK-1+ cells were T3+M1-. We propose that these subsets of cells represent different stages in NK cells differentiation.

Antigens, Surface↗

Characterization of HNK-1+ (Leu-7) human lymphocytes. II. Distinguishing phenotypic and functional properties of natural killer cells from activated NK-like cells.

HNK-1+ and HNK-1- lymphocytes from human blood were sorted with a fluorescence-activated cell sorter and compared for their phenotypic and functional properties. The HNK-1+ cells exhibited virtually no response to either mitogens (PHA, Con A, and PWM) or allogeneic cells, because the 3H-thymidine uptake for HNK-1+ cells was only 1 to 3% of that for HNK-1- cells. On the other hand, the HNK-1- cells responded efficiently to these stimuli and acquired a potent killing activity against K562 and other target cells after stimulation. The proliferating lymphoblasts did not acquire the HNK-1 antigen. These activated HNK-1- cells had a wider spectrum of spontaneous cytotoxicity than did HNK-1+ cells against 12 different target cells. Two distinct populations of effector cells for spontaneous killing can thus be distinguished on the basis of HNK-1 antigen expression. The classically defined NK cells are HNK-1+, whereas effector cells activated by either mitogens or allogeneic cells are HNK-1-. The HNK-1+ cells were not generated from the pool of HNK-1- cells under any of the culture conditions tested. The NK cells defined by the HNK-1 antibody are thus a functionally distinct population of cells. Although some HNK-1+ cells may also express T cell-associated antigens and sheep erythrocyte receptors, they lack some important functional properties ascribed to T cells.

Antigens, Surface↗

A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1).

A monoclonal IgM antibody (HNK-1) was produced against a membrane antigen from the cultured T cell line, HSB-2. By indirect immunofluorescence, this antibody reacted with certain human cultured T cell lines (HSB-2 and MOLT-4 but not MOLT-3) but not with other lines of B cell or phagocytic cell origin. HNK-1 reacted with 15.1 +/- 7.1% of normal blood lymphocytes but was unreactive with monocytes, granulocytes, erythrocytes, and platelets. HNK-1+ cells separated by a fluorescence-activated cell sorter (FACS) were a homogeneous population of medium sized lymphocytes with abundant neutrophilic cytoplasm containing azurophilic granules. HNK-1+ cells were nonadherent, surface Ig-, mostly FcIgG receptor+ and both positive and negative for demonstrable sheep erythrocyte (E) rosetting capability. Cell suspensions enriched for E-rosetting T cells and depleted of FcIgG receptor+ cells contained few (6%) HNK-1+ cells. Depletion of HNK-1+ cells from blood mononuclear cell populations by complement (C) mediated lysis greatly reduced NK activity against K-562 target cells and K cell lytic activity against antibody-coated chicken red blood cells. Treatment with HNK-1 alone or C alone did not affect these activities. When the FACS was utilized to separate HNK-1+ and HNK-1- cells from 6 individuals, the HNK-1+ cell population contained almost all of the NK and K cell function. The monoclonal antibody HNK-1 thus defines the first differentiation antigen shown to be selectively expressed on human NK and K cells.

Animals↗

Detection of monoclonal B lymphocytes in multiple myeloma by immunofluorescence tests of surface immunoglobulins.

Peripheral blood lymphocytes of 16 patients with secretory type of multiple myeloma and 5 with nonmyelomatous monoclonal gammopathy were investigated for the surface immunoglobulins on the cell by immunofluorescence. A low pH shock of cells before staining was applied to dissociate the passively absorbed immunoglobulins present on the cell surface. Increases of B lymphocytes bearing surface immunoglobulins which have the same light chains as those of monoclonal immunoglobulins produced by the plasma cells were found in 5 of 11 common secretory myeloma patients and in all of 6 Bence-Jones myeloma patients. Ratios of cells bearing light chains of kappa- and lambda-types (kappa/lambda) appeared abnormal in almost all with an exception of only 3 cases of myeloma patients, even in the cases where the number of Ig bearing cells did not increase. Increases of possible monoclonal B cells bearing IgG, in addition to IgA cells, were observed in some patients with IgA myeloma. Increases of B cells bearing certain heavy chains were also observed in all 5 patients with Bence-Jones myeloma during the course of disease. No abnormalities of B cells bearing surface immunoglobulin were found in nonmyelomatous monoclonal gammopathy. These results suggest that proliferation of monoclonal B lymphocytes, which may be progenitors to the malignant plasma cells, occurs in a majority of myeloma patients, but not in nonmyelomatous monoclonal gammopathy.

Adult↗

Studies of surface immunoglobulins on human B lymphocytes. III. Physiological variations of SIg+ cells in peripheral blood.

The levels of B lymphocytes bearing surface immunoglobulins in human peripheral blood were measured by immunofluorescence after pre-treatment of the cells with a low pH shock or washing at 37 degrees C. It was found that the percentages of SIg-bearing cells in an individual varied throughout the day and showed a circadian rhythm with a peak at 12 midnight and a depression at 12 noon. In addition, the levels of the B lymphocytes in the peripheral blood were shown to vary annually, being lower in the winter than in the summer.

Adult↗