Phorbol myristate acetate (pma) is a potent mitogen for human peripheral blood lymphocytes (PBL) comparable to phytohemagglutinin (PHA) in potency. Inactivation of PHA-responsive lymphocytes by 5'-bromodeoxyuridine and light treatment left the PMA response intact and nice versa. Experiments separating lymphocytes by rosetting with sheep erythrocytes (SRBC) demonstrated that the PMA-responsive lymphocytes segregate with those that have a high affinity for SRBC to a greater than PHA- or concanavalin A (Con A)-responsive cells. These results indicate that a PMA-responsive population in human peripheral blood resides within the T-lymphocyte population and appears to have a high affinity for SRBC and to be distinct from that responding to PHA and Con A. PMA may be useful clinically to assay the size and function of the high affinity or "active" rosette population.

Animals↗

PubMed1976

5-bromodeoxyuridine-light inactivation of human lymphocytes stimulated mitogens and allogeneic cells: evidence for distinct T-lymphocyte subsets.

The study of human peripheral blood currently permits enumeration of circulating B and T lymphocytes as well as the analysis of functional responses in vitro following stimulation with mitogens, antigens or allogeneic cells. In the present experiments, subsets of these major lymphocyte populations were analyzed by dissecting in vitro responses using an ablative technique. After an initial culture period of lymphocytes with a mitogen, the proliferating cells were inactivated with 5-bromodeoxyuridine and light, then the capacity of the remaining lymphocytes to respond to the same or a different mitogenic influence was tested. Responsiveness to a different stimulant in the presence of no further response to the first stimulant was taken as evidence for a different responding cell population. A large subset of peripheral blood lymphocytes was responsive to both phytohemagglutinin (PHA) and concanavalin A (Con A); ablation of the cells responsive to one left little or no cells responsive to the other. Pokeweed mitogen (PWM) stimulated a portion of the PHA-Con A-responsive subset and an approximately equal subset unresponsive to PHA or Con A. Other evidence indicates that with each of these mitogens (especially with PHA and Con A in a soluble form), most of the proliferative response of peripheral blood B lymphocytes is indirectly triggered and is dependent on T cell stimulation. The population of PHA-Con A-responsive cells is, therefore, interpreted to represent a major T cell subset plus recruited cells; the PWM-responsive population would include a T cell subset having also PHA and Con A responsiveness, and another subset of T (or perhaps B) cells. The mitogen-sensitive population showed no overlap with cells responsive to allogeneic stimulation in mixed leukocyte culture. Ablation of the mitogen-responsive cells potentiated the mixed leukocyte reaction, suggesting that a suppressive influence was removed with the inactivation of the mitogen-responsive cells. It appears, therefore, that distinct subsets of T lymphocytes differentially responsive to PHA-Con A, to PWM and to allogeneic stimulation are present in the human peripheral blood.

B-Lymphocytes↗

PubMed1976

Antilymphocyte antibodies:an approach to dissecting the heterogeneity of the immune system.

Antilymphocyte antibodies can be used to dissect the lymphocyte populations and subpopulations. In the mouse, at least seven gene loci govern the expression of allo-, hetero-and autoantigens at the surface of T-lymphocytes. The antisera, especially the alloantisera, permit definition of the differentiative state of cells and discriminate between subsets of T-cells with different functions. Less is known about human T-lymphocyte differentiation antigens and their genetic determinism. However, heterologous antisera specific for human T-cells have been prepared and their use has been of help in studying this cell population. The antigens recognized by such antisera are present at a higher concentration on thymocytes than on peripheral blood T-lymphocytes. They appear at the surface of bone marrow T-cell precursors after a short incubation with thymic factors. Such markers of T-lymphocytes in various stages of differentiation and the study of in vitro differentiation from precursor cells have already proven to be valuable tools for clinical investigation, especially in the realm of immunodeficiency diseases.

Animals↗

PubMed1975

Effect of thymic factors on the differentiation of human marrow cells into T-lympnocytes in vitro in normals and patients with immunodeficiencies.

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Adult↗

PubMed1975

T-lymphocytes and serum inhibitors of cell-mediated immunity in renal insufficiency.

In acute as well as chronic renal insufficiency significant immunological abnormalities were found: diminution of delayed hypersensitivity skin reactions, lymphopenia, reduction of the absolute but not relative number of peripheral blood T-lymphocytes. Responses of lymphocytes from uremic patients to PHA, allogeneic cells, or antigens were normal when lymphocyte cultures were preformed in allologous serum from a healthy individual. Sera from uremic patients had an inhibitory or toxic effect on stimulation of normal lymphocytes. Such an in vitro inhibitory activity was found not only in the whole serum but also when certain substances retained in renal failure (methylguanidine, larger molecules, etc.) were added in the lymphocyte cultures.

Acute Kidney Injury↗

PubMed1975

Immunodeficiency diseases. I. T-lymphocyte precursors and T-lymphocyte differentiation in partial Di George syndrome.

Immunological and pathological studies in a case of partial Di George syndrome revealed an absence of parathyroids, a major hypoplasia of thymus but a relatively moderate decrease in peripheral T-lymphocyte numbers and functions. After in vitro incubation with normal thymus extracts, a normal proportion of bone marrow cells was induced to differentiate into cells with characteristics of T lymphocytes, thus establishing the presence of T-cell precursors in the patient's bone marrow.

Antigen-Antibody Reactions↗

PubMed1975

Antiglobulin test for titration of antilymphocyte globulin.

An antiglobulin assay, derived from the indirect Coombs' reaction has been adapted to the titration of antilymphocyte globulin (ALG). Ten different ALG preparations have been investigated by this test and titres obtained are satisfactorily correlated with skin allograft survival in monkeys, rosette inhibition and mixed lymphocyte reaction inhibition. The antiglobulin test has also proved to be valuable for the monitoring of ALG-therapy in patients as well as for studying the mode of action of this potent immunosuppressive agent.

Agglutination Tests↗

PubMed1974