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Biomedical subjects

D M Strong

Publications and source records attributed to D M Strong.

At least 73 records · Page 4Linked to original sources

Immunologic characterization of a helper T-cell lymphoma.

The lymphocytes of a patient with a T-cell non-Hodgkin's lymphoma with peripheral blood involvement and polyclonal hypergammaglobulinemia were characterized in terms of surface markers and immunologic functions. Using the fluorescence-activated cell sorter and employing various monoclonal antibodies against T-cell surface antigens, it was shown that almost all of the patient's peripheral blood lymphocytes were positive for OKT4 and 9.3, antibodies that recognize helper T-cell subset. The circulating lymphoma cells had typical characteristics for T cells; they formed spontaneous rosettes with sheep erythrocytes and stained with the pan-T-cell antibodies 9.6 and 10.2, but did not react with other anti-T-cell monoclonal reagents such as OKT3, UCHT-1, and 3A1. The cells appeared to be mature by the fact that they did not stain with OKT6, and terminal deoxynucleotidyl transferase was undetectable. Functionally, they were able to provide "help" for antibody production, and they could be stimulated to produce moderate amounts of interleukin-2, while unable to proliferate in response to mitogens. Morphologically, some of the lymphocytes showed a deeply cleaved nucleus.

Aged↗

Flow cytometric analysis of normal and neoplastic human hematopoietic surface antigens.

Normal and neoplastic human hematopoietic cells were examined for surface markers by a variety of techniques including cytotoxicity assays using anti-HTLA and anti-Ia antiserum with viability measured by trypan blue exclusion and automated flow cytometry; E- and EAC-rosette binding assays and surface immunoglobulin measured by a fluorescence-activated cell sorter. In most cases there was good agreement among these assays. However, one case of CLL of T origin (92% E-rosette-positive) also showed significant amounts of Ia antigen by cytotoxicity tests; additionally, a case of CML in blast crisis demonstrated no E or EAC markers or surface immunoglobulin, but the majority of cells were lysed by both anti-HTLA and anti-Ia antiserum. Thus, Ia is not an exclusive B cell marker.

Animals↗

Antigenic characterization of a T-CLL with heteroantisera and monoclonal antibodies: evidence for the T cell lineage of an Ia-positive, Fc-IgG--positive, suppressor-cell subpopulation.

In a previous report, peripheral blood mononuclear T cells from a patient with T-chronic lymphocytic leukemia (T-CLL) were shown to bear receptors for the Fc portion of IgG (T gamma). Moreover, the ability of these cells to rosette with sheep erythrocytes was strongly inhibited by a preincubation of the cells with theophylline. These data indicated that they represent a highly purified subpopulation of Fc-IgG receptor-positive, low-affinity rosetting cells with in vitro suppressor activity on lectin-induced proliferation of normal lymphocytes. They also were reactive in antibody-dependent cell-mediated cytotoxicity but had no reactivity in natural killer cell assays. These cells were studied in this report with several heteroantisera and monoclonal antibodies. Results indicate that these T-CLL cells express a T cell antigenic pattern (OKT-3+) and the majority are Ia positive. They also react with the OKT-8 reagent (a reagent detecting the subset of T cells that contains the cytotoxic/suppressor cells), whereas they are negative with OKT-4 (which reacts with the subset of T cells that contains helper cells) and OKT-6 (thymocyte) antibodies. Heteroantisera also support the results obtained with monoclonal reagents. Despite some recent evidence showing that a high percentage of T gamma cells may belong to the monocyte-myeloid lineage, these T-CLL cells were negative with OKM-1, a monoclonal antibody reported to detect a monomyeloid antigen. These results suggest that a distinct subpopulation of suppressor T cells can be identified by membrane-marker phenotyping.

Adult↗

Clinical effects of infusions into chimpanzees of primed autologous cultured T-cells.

As a model to study the possible early side effects of cultured T-cells (CTC) as a potential for adoptive cellular immunotherapy of human tumors, chimpanzees received iv infusions of 10(9) autologous, mixed lymphocyte culture-primed CTC. Complete blood counts, urinalyses, chest X-rays, blood chemistries, and serum immunoelectrophoresis were normal, and serologic studies were negative throughout the 3 weeks of observation. Serial transaminase levels were followed in 2 chimps, and mild increases in serum glutamic-oxaloacetic transaminase were seen in both and serum glutamic-pyruvic transaminase in 1 at 24 hours following each CTC infusion, but the levels returned to normal within 7 days. A liver biopsy specimen was normal. Fluorescence-activated cell sorter analysis of cells incubated with day 28 serum revealed weak labeling of only phytohemagglutinin (PHA)-stimulated lymphoblasts and of CTC, suggesting that a weak anti-PHA antibody was generated. These studies indicate that infusions of autologous, in vitro-primed CTC are accompanied by little clinical toxicity in the chimp model but that they may be weakly immunogenic.

Animals↗

Lack of expression on cultured human T-lymphocytes of a T-cell antigen shared by the MOLT-4 cell line and normal human thymocytes.

Four hematopoietic cell lines (CCRF-CEM, HSB-2, MOLT-4, and RPMI-8402), derived from acute lymphoblastic leukemia and expressing T-cell surface markers (T-HCL), were studied with two specific anti-T-cell sera. The sera were raised in rabbits against human thymocytes (anti-HTY) and against T-cell cultured in the presence of conditioned medium derived from lymphocytes stimulated with PHA (anti-CTC). Both sera were absorbed to obtain a T-cell specific pattern of reaction and were further absorbed with normal peripheral blood lymphocytes or with each of the four T-HCL. The anti-HTY sera absorbed with CEM, 8402, and HSB-2 still reacted with MOLT-4. A similar pattern of reactivity was found only with the anti-CTC absorbed with 8402, whereas, after absorptions with the other cell lines, this antiserum was unreactive against MOLT-4. After absorption with normal peripheral blood lymphocytes, anti-HTY still reacted with thymocytes and MOLT-4 but was negative on CTC. In contrast, anti-CTC absorbed with peripheral blood lymphocytes (PBL) was negative on thymocytes and MOLT-4 but still reacted against CTC. Our data confirm the existence of a T-cell antigen (probably an early T-cell differentiation antigen) shared between thymus and MOLT-4. This antigen is not expressed on CTC, although these cells express an antigenic pattern more complex than PBL. Antisera to CTC represents a source of anti-T cell sera free of contamination with antibodies to early thymus-related antigens but containing other T-cell-related specificities.

Antigens, Surface↗

Anti-idiotype antibody in the primate. 1. Characterization and specificity against cells primed for histocompatibility determinants.

An anti-idiotype serum was raised in a chimpanzee (A) by immunization with autologous lymphocytes primed in vitro against an unrelated chimp (B). This autoantiserum in the presence of complement was cytotoxic for 5 to 7% of the resting lymphocytes from chimp A and for 30 to 45% of the mixed lymphocyte culture (MLC) primed cells (A X Bx), but was not reactive against the lymphocytes of the priming chimp (B). Anti-idiotype antibody and complement treatment of autologous resting or primed cells blocked the ability of these cells to respond in MLC or primed lymphocyte test (PLT) to the stimulator cells from chimp B, but not to cells from a third chimp. When cells from the immunized animal (A) were incubated with the autologous antiserum in vitro, they were stimulated, thus producing cells which had the same activity in PLT as did cells primed against stimulator cells of chimp B. Thus, an autoanti-idiotype serum has been raised in a primate system which identifies the recognition structure on autologous T cells directed against antigeneic determinants on the stimulator cells of a histoincompatible donor.

Animals↗

In vitro stimulation of human peripheral blood lymphocytes by soluble and membrane fractions of renografin-purified typhus group rickettsiae.

Cell-free extracts of disrupted Renografin-purified Rickettsia typhi and R. prowazekii were evaluated as antigens in lymphocyte transformation assays for cell-mediated immunity to typhus group rickettsiae in 19 individuals with and 9 without histories of exposure to these organisms. Exposure consisted of clinical disease, vaccination with epidemic typhus vaccine, or occupational exposure to these agents. Both the soluble and membrane fractions of disrupted purified rickettsiae were used, and transformation of peripheral blood lymphocytes (PBL) was determined in microcultures by incorporation of [(3)]thymidine. Of the antigen concentrations tested (1 to 400 mug/ml), 10mug/ml appeared to be the most satisfactory. At this concentration, PBL transformation was highly reproducible and correlated well with donor exposure and the presence of enzyme-linked immunosorbent assay anti-typhus group immunoglobulin G. At higher concentrations, PBL from both exposed and control donors often responded to a lipopolysaccharide-like component present in these preparations. Specific transformation responses to rickettsial fractions were detected in several individuals decades after infection or vaccination, indicating that both fractions contained antigens associated with persisting cell-mediated immunity in humans. Generally, stimulation indexes with the soluble fraction were slightly greater than those obtained with corresponding concentrations of the membrane preparation, and in three individuals transformation was observed only with the soluble fraction. PBL transformation to soluble fractions also appeared to have some species specificity, since PBL from individuals with documented R. typhi infections were more responsive to the homologous soluble preparation than to the soluble fraction of R. prowazekii. PBL transformation also correlated well with homologous but only poorly with heterologous enzyme-linked immunosorbent assay immunoglobulin G titers.

Antibodies, Bacterial↗

Evaluation of the immunogenicity of freeze-dried skin allografts in humans.

A study was undertaken to evaluate the antigenic potential of allogeneic freeze-dried skin (FDS) when used as a grafting material and to examine the clinical results when FDS is used for the correction of mucogingival problems in humans. FDS was obtained from an HLA-tissue-type donor according to Navy Tissue Bank protocol. Allogeneic FDS grafts were performed to correct mucogingival problems. In addition, periosteal fenestration was used in conjunction with approximately one-half of the grafts. Documentation with a standardized periodontal probe consisted of clinical measurements taken preoperatively and 8 weeks postoperatively. Blood samples were drawn prior to and at 1, 2, 3, 5, and 8 weeks postsurgically. Testing of blood samples for anti-HLA antibody was performed by use of a modified microcytotoxicity assay. Thirty-one patients received 36 FDS grafts involving 148 tooth sites. The FDS allografts resulted in a significant (P < 0.001) increase in the width of attached-type tissue (mean gain = 3.80 mm). Clinically, there was no sign of graft rejection, and serologically, all serum samples tested were nagative for the presence of anti-HLA antibody. FDS grafts used for the treatment of mucogingival problems in humans are nonimmunogenic as evaluated for anti-HLA antibody. The surgical procedure performed using FDS as a graft material resulted in a significant increase in the width of attached-type tissue.

Antibody Formation↗

Characterization of a suppressor T-cell chronic lymphocytic leukemia with ADCC but not NK activity.

A patient with T-cell chronic lymphocytic leukemia (T-CLL) is reported whose cells demonstrate in vitro suppression of normal lymphocyte mitogen stimulation. The patient, who remains in Rai's clinical stage 0 on no therapy after more than 24 mo of observation, has shown a less aggressive clinical course than is usually attributed to T-CLL. His peripheral blood lymphocytes (PBL) were characterized by functional assays as well as surface markers. Over 90% of the patient's PBL formed rosettes with sheep erythrocytes and were lysed by two T-cell-specific antisera plus complement, while less than 1% bore surface immunoglobulins, and only 3% had complement receptors. In addition, 45% of the PBL demonstrated Ia-like antigens, more than 50% expressed a receptor for the Fc portion of IgG(T gamma), and most of the sheep erythrocyte rosettes were inhibited by theophylline. The patient's cells failed to respond to several mitogens and they caused marked suppression of lymphoproliferative responses to normal PBL to phytohemagglutinin (PHA) and concanavalin A (Con-A). The patient's lymphocytes also exhibited antibody-dependent cytotoxic activity (ADCC) against antibody-coated nucleated target cells, but lacked demonstrable natural killer (NK) activity. This patient's T-CLL cells appear to represent the clonal expansion of a subset of T cells with a previously undescribed pattern of suppressor and cytotoxic activities.

Adult↗