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Biomedical subjects

E G Engleman

Publications and source records attributed to E G Engleman.

At least 181 records · Page 10Linked to original sources
PubMed1980

Functional characteristics of human T-cell subpopulations distinguished by a monoclonal antibody.

In animals and in man, diverse immunologic functions are mediated by specialized T-cell (thymus-derived lymphocyte) subsets that are distinguishable from one another on the basis of differences in cell surface determinants. Unfortunately, in humans, subset-specific antibodies have been difficult to generate. In this study, production of a murine monoclonal antibody specific for a subset of human T cells was achieved by fusing a sensitized B cell (bone marrow-derived cell) with a myeloma cell and isolating the antibody secreted by the resultant hybrid clone. This antibody binds 30-35% of peripheral T lymphocytes (T(a) (+) cells) but fails to bind remaining T lymphocytes (T(a) (-) cells), B lymphocytes, or monocytes. T(a) (+) and T(a) (-) subpopulations were separated with a fluorescence-activated cell sorter and their in vitro responses to various stimuli were assessed. T(a) (+) and T(a) (-) cells respond equally well to soluble antigens, allogeneic B cells, and autologous B cells, but only T(a) (+) cells respond to concanavalin A. T(a) (+) cells cultured in the presence of concanavalin A gradually lose the T(a) marker, an effect not observed after stimulation with phytohemagglutinin, soluble antigens, or alloantigens. These results suggest that the functional subpopulation of T cells defined by T(a) does not correspond to any previously described human T cell subset. Furthermore, somatic cell hybridization has been shown to be a feasible method for production of monoclonal antibodies specific for subpopulations of human lymphocytes.

Antigens, Surface↗
PubMed1980

Inhibition of cell mediated immune responses by 8-methoxypsoralen and long-wave ultraviolet light: a possible explanation for the clinical effects of photoactivated psoralen.

Human thymus-derived lymphocytes proliferate when cultured with lymphocyes or epidermal cells from unrelated individuals because such cells express HLA-D antigens, which are recognized as foreign by thymus-derived lymphocytes. The current study demonstrates that these responses are inhibited if either the stimulator cells or responder cells are pretreated with the combination of 8-methoxypsoralen and long-wave ultraviolet light. Additional studies revealed that photoactivated 8-methoxypsoralen has a lethal effect on lymphocytes and monocytes but not on the majority of epidermal cells. These obervations suggest that the dramatic beneficial effect of PUVA on patients with psoriasis and other skin disorders may be due to a toxic effect on immunocompetent cells in the epidermis, which results in inhibition of cell mediated immune responses.

Epidermis↗
PubMed1980

Autologous mixed lymphocyte reaction in patients with Hodgkin's disease. Evidence for a T cell defect.

The proliferative response of T lymphocytes cultured with autologous non-T lymphocytes is known as the autologous mixed lymphocyte reaction (MLR). This reaction can be demonstrated reproducibly in healthy individuals and has been shown to generate specific cytotoxic T cells, as well as T cells that regulate antibody synthesis and cell-mediated immunity. In this study, we demonstrate that the autologous MLR is impaired or absent in most patients with Hodgkin's disease regardless of age, sex, pathologic stage, or histologic classification. In 64 patients, the mean autologous MLR was 3,084+/-1,878 cpm compared to 16,552+/-6,532 in 29 healthy donors. A defect in autologous MLR was observed in newly diagnosed patients before the initiation of therapy, but was also found in patients without evidence of recurrent disease up to 15 yr after treatment. These findings could not be explained by abnormal kinetics or poor viability of stimulator or responder cells. The possibility that suppressor cells are responsible for the reduction of T cell autoreactivity was examined by comparing the autologous MLR of a healthy HLA-identical sibling in the presence and absence of T or non-T cells of an affected sibling. No inhibitory effects were observed. Similarly, substitution of patient plasma for pooled AB serum failed to inhibit the autologous responses of normal donors. Increasing the number of responder T cells in the culture or removing adherent cells from the stimulator population enhanced autoreactivity in some patients, indicating that the defect is not absolute. In two families, T cells of healthy HLA-A, B, and DR-identical siblings of patients responded normally to the non-T cells of their affected siblings, whereas patients' T cells failed to respond both to their own stimulator cells and those of their healthy HLA-identical siblings. These data indicate that the impairment of autologous MLR in some patients is due to a reduction or dysfunction of responder T cell activity and not to a defect of autologous stimulator cells.

Adolescent↗
PubMed1978

Suppression of the mixed lymphocyte reaction in man by a soluble T-cell factor. Specificity of the factor for both responder and stimulator.

J.H., an HLA-Dw2 homozygous multiparous woman, fails to respond to her husband, W.H. (HLA Dw1,-) in the unidirectional mixed lymphocyte reaction. T cells from J.H. were previously shown to suppress the responses of Dw2-positive cells but not Dw2-negative cells to W.H. We now report that a soluble factor released into the supernate of the mixed lymphocyte reaction by J.H. T cells, mediates this suppression. Like the cell from which it is derived, the factor is highly specific for HLA Dw2 in the responder cell and partially specific for the stimulatory alloantigen.

Antibody Specificity↗
PubMed1978

A suppressor T cell of the mixed lymphocyte reaction in man specific for the stimulating alloantigen. Evidence that identity at HLA-D between suppressor and responder is required for suppression.

It has previously been shown that J.H., a human leukocyte antigen (HLA)-Dw2 homozygous multiparous woman, fails to respond in a mixed lymphocyte reaction (MLR) to her Dw1 homozygous husband W.H., and that her T cells suppress the responses of HLA matched responders to W.H. The present studies take advantage of the observation that J.H. suppressor cells resist a dose of gamma-irradiation which functionally eliminates her MLR responder cells. J.H. cells, depleted of alloreactive cells, suppress the responses of Dw2 heterozygous or homozygous cells to W.H., regardless of their associated HLA-A or B antigens. Only when W.H. or a few other cells are present as the irradiated stimulator is J.H. suppression of Dw2 responses detected. Thus, the J.H. suppressor T cell recognizes determinants in the irradiated stimulator cells as well as D locus products in the responder.

Dose-Response Relationship, Radiation↗
PubMed1978

A suppressor T cell of the mixed lymphocyte reaction specific for the HLA-D region in man.

The mixed lymphocyte reaction (MLR) is the proliferative response of one individual's lymphocytes cultured in the presence of another individual's lymphocytes. In man, the MLR is elicited by cell surface antigens coded for by the HLA-D gene locus. This locus is among a cluster of genes which are located on the sixth chromosome and which include genes coding for the major histocompatibility antigens HLA-A, B, and C as well as HLA-D. If the stimulator cell possesses D locus antigens not present in the responder, the lymphocytes of the latter will undergo blast transformation resulting in DNA synthesis which can be measured. A vigorous response in the MLR to allogeneic cells is the rule among healthy individuals. We describe studies of a 23-yr-old man whose lymphocytes respond normally to mitogens and soluble antigens but fail to respond to allogeneic cells in the MLR. His medical history is unremarkable except that he received thymic irradiation as an infant. HLA typing revealed that he is homozygous for HLA-A2, B12, and Cw5 as well as for the D locus antigen Dw4. When his lymphocytes were added to the responder lymphocytes of other persons homozygous for the same HLA antigens, their responses to allogeneic cells but not mitogens were suppressed by 50-95%. Their responses to a soluble antigen, tetanus toxoid, were suppressed to a lesser degree. These inhibitory effects were mediated by a relatively radioresistant thymus-derived (T) lymphocyte. Further studies of the requirements for MLR suppression revealed that only persons heterozygous or homozygous for the Dw4 antigen were inhibited by the suppressor T cell. This effect was not altered by differences in the HLA-A, B, or C antigens between the suppressor and responder. It is concluded that genes in or near the HLA-D locus code not only for antigens (primarily on bone marrow-derived (B) cells), that elicit the MLR, but also for structures on T cells, or possibly macrophages, which are recognized by MLR suppressor T cells.

Adult↗
PubMed1977

Cellular immune reactivity in patients with rheumatoid arthritis and effects of levamisole.

Cellular immune reactivity was examined in control subjects and in 16 patients with rheumatoid arthritis before and after administration of levamisole. Prior to levamisole treatment, this population of patients with rheumatoid arthritis had diminished cellular immunity as measured by skin test reactivity, lymphocyte stimulation by antigen and by PHA, lymphocyte count and percentage and absolute numbers of long-incubation rosette-forming cells (RFC). Administration of levamisole caused enhancement of skin test reactivity and flares at dinitrochlorobenzene (DNCB) test sites which were not paralleled by an increase in lymphocyte stimulation by the same antigens in vitro or enhancement in the PHA response. The increase in lymphocyte count and RFC was borderline (p = .06). Of the 16 patients who received levamisole for three months, nine patients showed at least one physical sign of improvement, five patients remained unchanged, and two patients experienced progression of their disease.

Adult↗
PubMed1974

Attitudes toward women physicians. A study of 500 clinic patients.

A questionnaire was administered to 500 clinic patients and their replies about men and women physicians were analyzed. Ninety-six percent stated that the typical doctor is a man, and 78 percent expressed a preference for a male doctor. A significant number of patients said they would be unwilling to discuss certain subjects with a woman doctor or to follow her advice. Women physicians were considered less competent and less experienced than their male counterparts. Attitudes toward women doctors were correlated with patients' sex, age, ethnicity, occupation, and chief complaint. Most impressive statistically were the negative attitudes of Spanish-speaking patients and the positive responses of obstetrics and gynecology patients and black women patients. Patients who had previously consulted women physicians were more favorable toward them, suggesting that increased exposure may lead to reduced prejudice.

Adult↗