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T B Strom

Publications and source records attributed to T B Strom.

At least 307 records · Page 17Linked to original sources

Immunological properties of subcellular rat lymphocyte preparations. Primary allogeneic stimulation in vitro by fractions containing Ia (RT1-B), but not RT1-A antigens.

Rat thymocyte membrane fractions have been prepared which exhibit strain-specific primary mixed-lymphocyte reaction (MLR)-stimulating and Ia (RT1-B) antigenic properties. These preparations lack the antigenicity of classical, serologically-defined RT1-A (Ag-B) antigens, as defined by in vitro serologic assays. Furthermore, after immunization of allogeneic hosts, specific anti-Ia and MLR-blocking antibodies, but not anti-AgB, alloantibodies are elaborated. Thymidine suicide experiments show that the same clones respond to whole cells and the fragments made from those cells, and the response segregates appropriately in F2 progeny as a major histocompatibility complex (RT1)-linked phenomenon. Hence, it is possible to generate Ia-related allogeneic helper signals in primary, as well as secondary, in vitro responses, using subcellular membrane fragments that have restricted expression of RT1-B-, but not RT1-A-, encoded antigens.

Animals↗

Electrophysiology of T lymphocyte cholinergic receptors.

The presence of functional muscarinic-cholinergic receptors on at least some T lymphocytes is suggested by the existence of saturable, high-affinity, specific muscarinic binding in T cell-enriched, but not in B cell-enriched, cell suspensions and by observed cholinergic effects on lymphocytes, (e.g., increased lytic capacity of cytotoxic lymphocytes preincubated with muscarinic agents). In this study, we used flow cytometry and a fluorescent probe of membrane potential, the cyanine dye 3,3'-dihexyloxacarbocyanine iodide, to examine the effects of cholinergic agonists and antagonists on the membrane potentials of lymphocytes in T cell-enriched and B cell-enriched suspensions. Acetylcholine (AcCho) and carbamoylcholine (CbmCho) depolarized the membranes of T cells, but not of B cells; the maximal depolarization was produced by 10 nM AcCho or by 1 nM CbmCho. Depolarization following exposure to these concentrations of agonists was maximal by 5-8 min; T cell membrane potentials returned to control values by 13-15 min. Less marked depolarization was produced by 100 nM AcCho and 10 nM CbmCho; 100 pM CbmCho was only slightly less effective than 1 nM CbmCho, and the depolarization persisted 12 min after exposure. Depolarization induced by 1 nM AcCho was abolished when AcCho was combined with 10 nM atropine but not when AcCho was combined with 1 nM atropine or 200 nM d-tubocurarine. The time course of the membrane potential response and its dependence on the relative concentrations of AcCho and specific cholinergic blocking agents correlate well with both binding studies and biological effects. Our results provide evidence that T lymphocytes have functional muscarinic receptors; the flow cytometric method should be generally applicable to studies of the electrophysiology and pharmacology of receptor-ligand interactions.

Acetylcholine↗

Transfer of specific unresponsiveness to organ allografts by thymocytes. Specific unresponsiveness by thymocyte transfer.

Prolonged survival of vascularized organ allografts has been produced in unmodified inbred rats by transfer of thymocytes from enhanced, engrafted, syngeneic animals. For these thymocytes to increase significantly the survival of test allografts they must be harvested 6-9 d after transplantation. Thymectomy of the enhanced, engrafted animals during the same critical period causes acute rejection of othewise long surviving grafts. For optimal effect, the enhanced thymocyte donor must be actively and passively immunized and receive a cardiac allograft. The necessity for erythrocytes in the initial active immunization regimen is noted. Additionally, the antigenic specificity of the suppressor effect has been established with two histoincompatible donor rat strains. Cellular and humoral host responses mounted by test graft recipients after thymocyte transfer from enhanced, engrafted donors are different from those mounted either by unmodifed animals acutely rejecting their grafts or by enhanced rats bearing well-functioning grafts. Numbers of T lymphocytes are reduced in the grafted hearts and in the spleens of test graft recipients, a finding paralleled by the complete absence of specific direct lymphocyte-mediated cytotoxicity. In contrast, cytotoxic antibody production, although delayed, is increased in magnitude, peaking around the time of graft rejection. These studies provide evidence that different biological manipulations can modify separate pathways in the complex cellular and humoral responses towards organ allografts. They demonstrate that cellular immunity is critically involved in immunological enhancement of vascularized organ allografts, a phenomenon hitherto considered primarily humoral. It seems clear that cells with suppressor activity are present within the thymus during the early phases of immunological enhancement.

Animals↗

Rejected human renal allografts: recovery and characteristics of infiltrating cells and antibody.

Viable infiltrating host leukocytes have been isolated from 10 rejected human renal allografts, removed 1 to 67 months after transplantation. The cell populations have been identified by surface characteristics and their cytotoxic capacities were assessed. A heterogenous population of cells of host origin accumulated in the grafts, including T and B lymphocytes, Fc+ cells, and macrophages. Using a 51Cr release assay, specific cytotoxicity against donor alloantigens was determined. Cytotoxicity of the infiltrating cells was almost invariably greater than cytotoxicity mounted by recipient peripheral blood lymphocytes. Deletion studies confirmed previous work and suggested that T cells were primarily responsible for cytolysis in early acute rejection; non-T cells more often in late chronic rejection. Antibodies eluted from the grafts demonstrated both specific antidonor and nonspecific activity as well as cross-reacting anti-HLA activity. Allograft morphology was examined and cellular and humoral host responses were assessed. These studies emphasize the complexities of immune responses produced by the host against transplanted tissues.

Antibody Specificity↗

Improved B cell typing for HLA-DR using nylon wool column enriched B lymphocyte preparations.

A rapid, simple procedure for preparing B lymphocytes using nylon wool has been devised. When mixtures of T lymphocytes, B lymphocytes, and monocytes are applied to nylon wool columns, B lymphocytes can then be removed, virtually free of monocytes. Such preparations (Ad) are 85 +/- 6% SIg+ and have only 3 +/- 1% monocyte contamination. The yield from peripheral blood averages 5% of all mononuclear cells. In contrast, the E rosette depletion method (E-) yields cells which are only 64 +/- 5% SIg+ and have 25 +/- 7% monocyte contamination. The superiority of the nylon method for HLA-DR typing was demonstrated in a comparative study of Ad and E- with eight normal individuals. Cytotoxic scores were higher and a large number of reactions, representing DRw groups and additional cross-reactions, was detected.

B-Lymphocytes↗

Factors contributing to the declining mortality rate in renal transplantation.

Recent modifications and refinements in the management of patients with renal allografts have diminished the mortality rate at our hospital to 2 per cent and 5 per cent at one year for patients receiving kidneys from related and cadaveric sources, respectively. Of 186 receiving transplants since 1974, seven (4 per cent) have died within one year of operation. The incidence of wound infections has been reduced from approximately 25 per cent in 1972 to 2 per cent since 1976 by the use of a single high dose of broad-spectrum antibiotics administered at the time of induction of anesthesia for any surgical procedure. Risk and limitations of immunosuppression have been better appreciated, ultrasound is used more often in the diagnosis of partial obstruction or perinephric fluid collections, and needle biopsy of the transplanted kidney has reduced the morbidity inherent in open biopsy. The contribution of sepsis as a cause of death has declined. The diminishing hazard of renal transplantation has made it an increasingly attractive treatment for end-stage kidney disease.

Anti-Bacterial Agents↗