Monoclonal antibodies for clinical investigation of human T lymphocytes.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R L Edelson
Publications and source records attributed to R L Edelson.
Peripheral blood of patients with cutaneous T-cell lymphoma: studies using monoclonal antibodies.
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
Interaction of T-lymphocytes with the epidermis: immunopathological studies.
Explore the source record for details and available documents.
Animals↗
Antigenic modulation of pan-T-cell and T-cell subset-specific markers.
The time course and extent of antigenic modulation induced by monoclonal antibodies OKT3, OKT4, OKT8, BE2, and BE3 was investigated. OKT3-induced antigenic modulation could be detected as early as after 3-hr incubation with the antibody and almost total removal of the OKT3-reactive antigen was seen by 42 hr. This modulation did not decrease the expression of T-cell antigens detected by OKT4 and OKT8. OKT3-modulated cells reexpressed the antigen after 42-hr incubation in OKT3-free media. BE3 (homologue of OKT1) also caused modulation of its surface antigen after 24-hr incubation. In contrast, OKT4 did not induce modulation even after 42-hr incubation with high concentrations of OKT4 antibody. Approximately 43% of the OKT8-reactive lymphocytes could be induced to modulate this antigen. A tumor-associated antigen present on neoplastic lymphocytes from patients with cutaneous T-cell lymphoma, recognized by monoclonal antibody BE2, also was not induced to modulate. These results suggest that antigenic modulation and the fate of the modulated antibody may be of importance to immunotherapeutic applications of these reagents.
Animals↗
Recognition of immature T-cell phenotypes in neonatal blood using monoclonal antibodies.
The monoclonal antibody reactivity of cord blood mononuclear cells to six monoclonal reagents, OKT3, OKT4, OKT6, OKT8, OKT10, and OKT11, was evaluated using an indirect immunofluorescence technique. An immature population of cells was found; 24% of T cells in cord blood expressed OKT6 and 58% expressed OKT10. A previously undescribed phenotype, OKT3+/OKT6+, was discovered using double-labeling studies. In addition, the OKT4+:OKT8+ ratio in cord blood was 1:2, compared with 1:3 in the normal adult controls tested in this study. This is explained by the presence of a population of OKT4+/OKT8+ cells circulating in the neonate. Double-labeling studies of the cord blood samples demonstrated that all of the OKT3+ cells were simultaneously OKT11+ and that 17% of the cells were OKT11+ only. This is in accordance with the findings in normal adult peripheral T cells. Therefore, circulating neonatal T cells express an immature phenotype more characteristic of thymocytes and an altered OKT4+:OKT8+ ratio as compared with adult controls. We also describe a new phenotype OKT3+/OKT6+ present on the cord mononuclear cells.
Adult↗
Cutaneous T cell lymphoma.
Explore the source record for details and available documents.
Administration, Topical↗
In situ identification of Langerhans cells in the dermal infiltrate of cutaneous T cell lymphoma.
A population of cells showing the surface phenotype of Langerhans cells (LCs) was identified in the dermal infiltrates of cutaneous T cell lymphoma (CTCL). Peroxidase-conjugated OKT6, a monoclonal antibody reactive with epidermal LCs, was used to directly label frozen tissue sections of diseased skin from twenty-three patients with CTCL, two patients with secondary cutaneous involvement by a B cell lymphoma, and three patients with lymphocytoma cutis. OKT6-reactive cells represented a significant although minor population in the dermal infiltrate of twenty-two of the twenty-three CTCL biopsies, accounting for up to 5% of the cells. Double-labeling studies revealed that the OKT6-positive cells also exhibited Ia but not T cell antigens. Since OKT6-reactive cells were not found in either the B cell lymphomas or lymphocytoma cutis, their presence in a malignant infiltrate is suggestive of a T cell neoplasm.
Fluorescent Antibody Technique↗
Immunoelectron microscopic identification of Langerhans cells using a new antigenic marker.
The specificity of a monoclonal antibody (OKT6) for epidermal Langerhans cells was examined by immunoelectron microscopy. Peroxidase-labeled OKT6 bound to 1-5% of suspended human epidermal cells, as determined by light microscopy. Electron microscopic examination of peroxidase-labeled cells revealed that all Birbeck granule-containing Langerhans cells bound OKT6. In addition, a small population of indeterminate cells, lacking the Birbeck granule, was also labeled with OKT6. The ultrastructural studies confirm the specificity of OKT6 for Langerhans cells and suggest that the indeterminate cell represents a related cell population.
Antibodies, Monoclonal↗
Interaction of T cells with the epidermis.
Explore the source record for details and available documents.
Animals↗
Diagnosis of cutaneous T cell lymphoma by use of monoclonal antibodies reactive with tumor-associated antigens.
Two murine monoclonal antibodies (BE1 and BE2), produced by using leukemic helper T cells from a patient with cutaneous T-cell lymphoma (CTCL) as immunogens, reacted selectively with CTCL lymphocytes and some transformed cultured lymphocytes, as determined by radioimmunoassay (RIA) and indirect immunofluorescence (IIF). BE1 reacted significantly (P less than or equal to 0.001) with leukemic CTCL lymphocytes and with CTCL cells from infiltrated lymph nodes (RIA, mean +/- SD = 776 +/- 275 cpm), as compared with background counts (263 +/- 68). BE1 binding to normal blood mononuclear cells (RIA, mean +/- SD = 283 +/- 58 cpm) was indistinguishable from background. BE1 also reacted with Epstein-Barr virus (EBV)-transformed B-cell lines (RIA, mean +/- SD = 794 +/- 230) and some long-term T-cell lines. BE1 did not react with the majority of lymphoid cell lines or tumor cell lines tested. BE1 also did not react with any normal tissues screened by IIF. BE1 precipitated a molecule from CTCL cells that, under reducing conditions, has two components with molecular mass of 27,200 and 25,800 D. BE2 also reacted significantly (P less than or equal to 0.001) with CTCL cells from two of four patients (RIA, mean +/- SD = 519 +/- 113 cpm). The binding of BE2 to normal mononuclear cells was indistinguishable from background (309 +/- 38 cpm). BE2 also reacted with an antigen present on EBV-B-cell lines (RIA, mean +/- SD = 654 +/- 194) and MOLT 3 and HUT 78 T-cell lines. BE2 reacted with an antigen expressed on a subpopulation of lymphocytes from five of eight patients with B-cell CLL studied by IIF (mean +/- SD = 18 +/- 6). Other long-term T-cell lines and tumor cell lines studied by IIF were unreactive with BE2. BE2 did not react with any of the normal tissues studied. BE2 precipitated a molecule (78,000 D) from CTCL cells and EBV-B cells with a single component under reducing conditions. Immunoperoxidase-labeled BE1 and BE2 reacted with CTCL cells in frozen sections of infiltrated lymph nodes and skin. In addition, BE1 and BE2 reacted with blood lymphocytes from 16 of 21 patients whose CTCL had otherwise been considered localized to skin. These two monoclonal antibodies react with tumor antigens associated with CTCL and appear to be useful in the diagnosis of this disorder.
Antibodies, Monoclonal↗
Biochemical characterization of a differentiation antigen shared by human epidermal langerhans cells and cortical thymocytes.
Previous immunofluorescent studies have shown that differentiation antigens recognized by the monoclonal antibody (OKT6) are present on the external membranes of human epidermal Langerhans cells, cortical thymocytes and some cultured T cell lines. In the present investigation, the biochemical characteristics of the OKT6 recognized antigens derived from these three sources were compared. Following immunoprecipitation with OKT6, a single band with an approximate molecular weight of 52,000 daltons was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (under both reducing and nonreducing conditions) in the detergent lysate of radioiodinated normal epidermal cells. A molecule with the same apparent molecular weight was immunoprecipitated from thymocytes and cultured MOLT-3 (T cell-acute lymphoblastic leukemia) cells. However, a low molecular weight protein of approximately 10,000 daltons was coprecipitated from these MOLT-3 cells. No electrophoretically identifiable antigens were precipitated from peripheral lymphocytes or monocytes with OKT6. These observations further distinguish Langerhans cells from classical monocytes, indicate that these cells express a membrane antigen otherwise characteristic of cortical thymocytes, and suggest the potential usefulness of the monoclonal antibody, OKT6, in further investigations of the functions and ontogeny of Langerhans cells.
Animals↗
Use of Orthoclone monoclonal antibodies in the study of selected dermatologic conditions.
Monoclonal antibodies recognizing human T cell differentiation antigens were used to study lymphocyte populations in three cutaneous diseases. Neoplastic lymphocytes from patients with varying phases of cutaneous T cell lymphoma (mycosis fungoides, Sezary syndrome and related presentations) were reactive with OKT1 and OKT3 (pan T cell reagents) and OKT4 (an antibody defining the functional "helper" T cell subset). The malignant cells lacked membrane antigens reactive with OKT5 and OKT8 (markers of "suppressor" T cells). The presence of an OKT1+, OKT3+, OKT4+, OKT5-, OKT8- phenotype on the neoplastic T lymphocytes of cutaneous T cell lymphoma (CTCL) supports the clinical impression that all phases of CTCL represent a single disease entity. A patient with pemphigus vulgaris, a disease of autoreactive, antiepidermal antibodies was shown to consistently have a marked expansion of the peripheral blood OKT4 reactive T lymphocyte population. These findings suggest that autoantibodies in pemphigus vulgaris may occur in the context of a profound OKT4/OKT5 immunoregulatory imbalance. Peripheral blood lymphocytes from patients ith extensive psoriasis vulgaris had a normal profile of reactivity with the OKT antibodies. In addition, OKT6 (marker of intrathymic T cells) has been shown to react with Ia+ dendritic cells in the epidermis suggesting that this antibody may recognize Langerhans' cells.
Adolescent↗
Normal numbers of phenotypic helper, suppressor, and total T cell populations in psoriasis vulgaris: quantitation by monoclonal antibodies.
Previous studies of E rosette-forming cells in the blood of patients with psoriasis vulgaris have demonstrated conflicting results. Availability of a battery of monoclonal antibodies permitted quantitation of individual T cell populations in patients with psoriasis. Peripheral blood mononuclear leukocytes from twelve patients with extensive, active psoriasis and from fifteen normal controls were studied by indirect immunofluorescence. No statistically significant differences from control values were identified (p values were all greater than or equal to 0.4). These monoclonal antibodies provide highly specific reagents, previously not available, for identifying different lymphocyte phenotypes. Analysis of the data indicates that shifts in major T lymphocyte subpopulations are not present in patients with active psoriasis.
Adult↗
Induction of lymphocyte differentiation by epidermal cultures.
Human and murine lymphoid cell populations were induced to express terminal deoxynucleotidyl transferase, a marker of early lymphoid differentiation, by exposure to allogeneic or syngeneic epidermal cells. Control growth medium, fibroblasts, or a mammary epithelial cell line did not induce this marker. These findings suggest that epidermal cells can induce lymphoid cell differentiation in vitro.
Animals↗
Cutaneous T cell lymphoma: characterization by monoclonal antibodies.
Monoclonal antibodies to human T cells permit the characterization of the surface phenotype of cutaneous T cell lymphoma (CTCL). The majority of CTCL cells are reactive with OKT1 and OKT3 monoclonals, which identify peripheral T cells and mature thymocytes. The neoplastic cells also react with OKT4, which recognizes the inducer T cell subset; they are, however, unreactive with OKT5 monoclonal, which identifies cytotoxic/suppressor T cell subsets. These data are in agreement with previous functional studies demonstrating that CTCL is a neoplasm of inducer (helper) T cells.
Antibody Specificity↗
Cutaneous T cell lymphoma: mycosis fungoides, Sézary syndrome, and other variants.
Cutaneous T cell lymphoma (CTCL) is a clinically and immunologically defined neoplasm which encompasses epidermotropic (mycosis fungoides, Sézary syndrome) and nonepidermotropic variants. A natural evolution apparently occurs from the epidermotropic to the nonepidermotropic form. In this review, cellular properties of the neoplastic cells are correlated with specific clinical observations, and recent therapeutic advances are discussed. Advances in our understanding of the pathogenesis of CTCL, including preliminary evidence suggesting that keratinocytes may elaborate a hormonal substance capable of inducing T lymphocyte differentiation, are discussed.
Female↗
Round cells of the epidermis: clues from studies on neoplastic lymphocytes of cutaneous T cell lymphoma.
Neoplastic cells of cutaneous T cell lymphoma (CTCL) appear to be of monoclonal origin and frequently are nonspecific helpers of normal B cell differentiation. A natural progression from epidermotropic (mycosis fungoides and Sézary syndrome) to nonepidermotropic, more widely disseminated T cell neoplasms generally occurs. Affinity of CTLC cells for the epidermis may result from their having membrane receptors for histocompatibility (Ia) antigens present in skin. Cultured human epidermal cells produce a thymopoietin-like molecule, an indication of a role for skin in T cell differentiation.
Animals↗