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H Levine

Publications and source records attributed to H Levine.

At least 127 records · Page 7Linked to original sources

Uniform detection of immunoglobulin-gene rearrangement in benign lymphoepithelial lesions.

The term "benign lymphoepithelial lesion" is used to describe the salivary-gland lymphocytic infiltration and epithelial changes typically found in association with Sjögren's syndrome. We used Southern blot hybridization techniques to examine the immunoglobulin genes in salivary-gland tissue derived from eight patients with benign lymphoepithelial lesions. Three of these patients had intrasalivary non-Hodgkin's lymphoma complicating the lesions, whereas the lesions in the remaining five were all histologically benign. Ten samples from the eight patients all revealed rearrangement of both the heavy-chain and light-chain immunoglobulin genes. In one of the patients in whom non-Hodgkin's lymphoma involved both the salivary-gland lesion and an ipsilateral lymph node, the rearrangements of the heavy-chain and light-chain immunoglobulin genes detected at the two sites were identical. One other patient had two distinct benign lymphoepithelial lesions removed two years apart. The rearrangements of the heavy-chain as well as the kappa light-chain genes detected in these two lesions were entirely different. These data suggest that B-cell clonal expansion has an integral role in the pathophysiology of the benign lymphoepithelial lesion and may explain the increased incidence of lymphoma noted in association with this disorder.

Adult↗

Undifferentiated leukemia of infancy with t(11:17) chromosomal rearrangement. Coexpressing myeloid and B cell restricted antigens.

It has been suggested that the malignant transformation, in some of the acute leukemias, may involve totipotent stem cells resulting in a biphenotypic leukemia expressing both myeloid, and lymphoid characteristics. We describe here a hybrid cell acute leukemia, in a 16-day-old infant, in whom leukemic cells coexpressed myeloid and lymphoid B cell antigens. Blast cells in the bone marrow showed L2 morphology according to the French American British (FAB) classification, with positive periodic-acid Schiff, and nonspecific esterase staining. Sudan black, and specific esterase were negative. Terminal deoxynucleotidyl transferase, was strongly positive in 5% of blasts, and faintly reactive with the rest. Karyotypic analysis demonstrated a translocation of t(11:17);(q23;p13). Immunoglobulin gene analysis revealed rearrangement of the heavy chain genes. The blasts' phenotype was HLA/DR+ B4+ My7+ My9+ common acute lymphoblastic leukemia antigen (CALLA) B1- T11-. Dual immunofluorescence staining using anti My7, and My9 fluorescein isothiocyanate, and anti B4 pycoerythrin conjugated monoclonal antibodies, and flow cytofluorometry, revealed a labeling pattern of 25% B4+; 10% to 15% My7+; 17% My9+; and 50% of cells coexpressing B4 My7, and My9 antigens. These results provide evidence for a hybrid leukemia with lymphomyeloblasts being part of a single clone, which may indicate the origin of this leukemic clone from a pluripotent (lymphoid/myeloid) stem cell.

Antibodies, Monoclonal↗

Development of natural killer cells in human thymocyte culture: regulation by accessory cells.

In vitro culture of human thymocytes resulted in the development of cells with natural killer (NK) activity and the acquisition of a pan-NK antigen (NKH1) by a large number of thymocytes. The ability to kill the NK-sensitive target, K562, was restricted to thymocytes expressing the NKH1 antigen. All NKH1+ thymocytes displayed a mature T cell phenotype, T3+T11+T8+T4-. Both the acquisition of NK activity and the development of cells with the NKH1+ phenotype could be suppressed by culturing thymocytes in the presence of adherent mononuclear cells. These results suggest that adherent accessory cells have the ability to regulate the development of T cell lineage NK cells.

Antibodies, Monoclonal↗

Characterization of the T3+T4+T8+ thymocyte intermediate in vitro.

Sensitive two-color fluorescence staining and cell-sorting techniques were used to isolate a T4+T8+ thymocyte subpopulation with high T3 density from human thymocyte cultures. Previously, this population was shown to give rise to both T4+T8- and T8+T4- thymocytes. In the present study, this T3+T4+T8 population was shown to be functionally as well as phenotypically distinct from either T8+T4- cells or T4+T8- cells present in the same culture. The T3+T4+T8+ cell had intermediate cytotoxic capacities relative to T8+T4- and T4+T8- thymocyte fractions. The proliferative capacity of the T4+T8+ population although less than that of the T8+T4- subset exceeded the proliferative response of the T4+T8- population. The time of appearance of large numbers of T3+T4+T8+ cells in culture as well as functional properties exhibited by T3+T4+T8+ cells are consistent with the notion that the T3+T4+T8+ cell represents an activated intermediate in thymocyte differentiation. The T3+T4+T8+ thymocyte may be an important intermediate in in vivo as well as in in vitro thymic differentiation. Moreover, the analysis of its functional properties may contribute to an understanding of functional responses exhibited by the most mature (T3+) population isolated from human thymus.

Antigens, Differentiation, T-Lymphocyte↗

Human thymocyte subpopulations: maturational stages defined by the expression of the T3-T cell receptor complex.

Using sensitive fluorescence flow-cytometric techniques, human thymocyte subpopulations were fractionated according to their surface expression of the T3-T cell receptor (T3-Ti) complex. Two major subpopulations, one expressing low (immature subpopulation) and one high T3 antigen surface density (mature fraction) were characterized in detail with respect to surface antigen expression, right-angle scatter and proliferative capacity. Thymocyte subpopulations were activated through the T11 molecule (alternate pathway) and compared with regard to interleukin-2 (IL-2) receptor expression, changes in right-angle scatter and 3H-thymidine incorporation. We report that both populations could be activated through the T11 pathway to undergo nuclear activation and express IL-2 receptors. Moreover, in the absence of accessory cells, only the most mature population, expressing high T3 density, could be induced to proliferate, whereas immature cortical thymocytes required accessory cells for proliferation. These findings suggest that the cellular microenvironment may have a critical role in regulating the activation of immature cortical thymocytes.

Antigen-Presenting Cells↗

A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody.

The cell surface phenotype of peripheral blood lymphocytes (PBL) of systemic lupus erythematosus (SLE) patients was characterized with the anti-2H4 monoclonal antibody that defines the human suppressor inducer subset. The T4+2H4+ population of cells has been shown to be critical for the activation of T8+ suppressor cells. Patients with SLE has a markedly decreased percentage of T4+2H4+ cells (13 +/- 2%) in their PBL compared with normal controls (21 +/- 1%) (P less than 0.001). This reduction was greatest in patients with active SLE, especially those with renal disease. Serial analysis of patients with SLE and renal disease showed a correlation between percent positive circulating T4+2H4+ cells and disease activity. Moreover, there was a significant correlation between a low percentage of T4+2H4+ cells and decreased suppressor-inducer function in autologous mixed lymphocyte reaction-activated T4+ cells from SLE patients. Thus, a deficiency exists in SLE patients with active renal disease in the T4+2H4+ suppressor-inducer T cell subset.

Adolescent↗

Expression of B cell activation antigens on normal and malignant B cells.

In an attempt to relate the functional events of B cell activation with changes in cell surface molecules, we have used a panel of monoclonal antibodies directed against cell surface antigens expressed on activated but not resting B cells, to determine a sequence of activation antigen expression following anti-immunoglobulin stimulation. Within the first 24 hr of culture with anti-Ig, resting splenic B cells were induced to express B5 and interleukin-2 receptor (IL-2R) and subsequently express T9 and BB1 by 48 hr. Maximum antigen expression was seen by day 3 with the majority of cells expressing B5, IL-2R, T9, and BB1, and fewer numbers of cells expressing Blast-1 and Blast-2. By day 6, the expression of these antigens significantly decreased. Dual fluorochrome staining of anti-Ig activated B cells demonstrated heterogeneity of activation antigen expression, suggesting the existence of subpopulations of activated B cells. In an attempt to relate the non-Hodgkin's lymphomas (NHLs) to this sequence of activation, 69 tumor samples from patients with B cell NHLs were then examined for expression of these activation antigens. Histologically defined subgroups of B cell NHLs demonstrated differential expression of activation antigens with B5, BB1, and T9 exhibiting the widest distribution, whereas IL-2R, Blast-1, and Blast-2 demonstrated more limited expression. The finding that no B cell malignancy phenotypically resembles the small resting B lymphocyte coupled with the observation that virtually all B cell NHLs examined expressed activation antigens suggests that these tumors may be the neoplastic counterparts of subpopulations of activated B lymphocytes.

Antibodies, Monoclonal↗

Biosynthesis and surface expression of T8 by peripheral blood T4+ cells in vitro.

Biosynthetic labeling with 35S-methionine and 35S-cysteine of isolated T4+ cells from Con A-activated T cells demonstrated that the T8 antigen was synthesized by activated T4+ cells. Two-color fluorescence analysis of the activated T cell population from which the T4+ fraction was obtained showed that both T4+T8- and T4+T8+ cells were present. The T8 antigen that was immunoprecipitated by monoclonal anti-T8 from activated T4+ cells migrated with an electrophoretic mobility corresponding to an m.w. of approximately 33,000, a previously reported m.w. value for T8 antigen. Con A activation of highly purified peripheral T4+T8- and T8+T4- subsets indicated that both T4+T8- and T8+T4- cells can give rise to T4+T8+ cells. However, substantial T4, T8 coexpression by T4+T8- cells required a signal from T8+T4- cells which could be supplied by incubating T4+T8- cells with irradiated T8+ cells or the supernatant from Con A-activated T8+T4- cells. The generation of T4+T8+ cells from a subset of T4+T8- T cells may be an important mechanism in immune activation and/or the further differentiation of peripheral T4+ cells.

Antigens, Differentiation, T-Lymphocyte↗

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Journal Article↗

Human thymocyte maturation in vitro: a flow cytometric analysis.

Using an in vitro culture system, light scatter analyses, and two-color flow cytometry, we provide evidence that the interleukin-2 (IL-2) and transferrin receptors can be induced within 48 hr on nonproliferating immature thymocytes. The thymocytes (greater than 35%) that expressed the transferrin and IL-2 receptors demonstrated nuclear activation as measured by log 90 degrees light scatter analysis. Increases in antigen-receptor-associated T3-antigen expression followed transferrin and IL-2-receptor induction and occurred on maximally activated T4+T8+ thymocytes on Day 3 of culture. Maximal T3 expression did not occur until Days 5-7 and paralleled loss of T4, T8 coexpression, suggesting an association between a mature T3-Ti antigen receptor complex and a mature T4, T8 phenotype.

Antigens, Differentiation, T-Lymphocyte↗

Expression of the NKTa clonotype in a series of human natural killer clones with identical cytotoxic specificity.

Over a period of 3 yr, a series of ten NK clones that express a unique clonotypic T cell receptor-like structure, termed NKTa, has been generated from a single individual. These clones were derived from either peripheral blood nonadherent cell fractions (JT9, JT10, JT11), NKH2-purified cells (CNK8, CNK9), or NKTa-purified cells (CNK11, CNK12, CNK13, CNK14, CNK15). Flow cytometric analysis of peripheral blood mononuclear cells from this individual showed that NKTa+ cells occur with a frequency of approximately 0.15%. The existence of NKTa+ cells in peripheral blood was confirmed by use of immunorosette enrichment techniques, flow cytometric purification, and subsequent clonal expansion of NKTa+ cells. Phenotypic analysis of NKTa+ clones showed that all expressed NKH1 as well as T3, T8, T11, T12, and Mo1 antigens. Only five of ten clones expressed NKH2 antigen. All NKTa+ clones had broad cytolytic activity against a series of seven different target cells that was similar to that of other NK clones. In addition, cytotoxicity of each clone could be inhibited by preincubation of effector cells with monoclonal anti-NKTa or by preincubation of target cells with monoclonal anti-TNKTAR. Although half of the NKTa+ clones appeared phenotypically different from the other half with regard to the expression of NKH2 antigen, analysis of T cell receptor gene rearrangements indicated that all NKTa+ clones contained identical gene rearrangements of C beta 2.

Antibodies, Anti-Idiotypic↗

Discrete stages of human thymocyte activation and maturation in vitro: correlation between phenotype and function.

Using light scatter, flow cytometric and functional analyses, three major stages in the in vitro activation of human thymocytes were defined. The earliest stage (day 0-2) was characterized by the induction of the interleukin 2 (IL2) and transferrin receptors, the T cell lineage specific Ta1 antigen, and increased reactivity with anti-T8 antibody. At this time, major changes in nuclear morphology but not cell size were observed. Early-stage thymocytes were immature with regard to T3 and cytotoxic capacities. The second stage (day 3-4) of in vitro culture was distinguished by loss of T6, maximal activation (both in cell size and nuclear morphology) and maximal expression of both transferrin and IL2 receptors. At this stage, nearly all thymocytes expressed T3, 30-70% of thymocytes were T4+T8+, and functionally, only small increases in cytotoxic capacities were observed. The third stage of maturation (day 5-7) represented thymocytes with reduced levels of activation as measured by forward and right angle light scatter analysis and declining IL2 and transferrin receptor expression. However, these thymocytes exhibited high levels of T3 antigen density, loss of T4, T8 coexpression and pronounced cytotoxic and detectable inducer function capabilities.

Antibodies, Monoclonal↗