An analysis of lymphocytes with both T-cell marker and IgG or complement receptors in patients with X-linked agammaglobulinemia.
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Agammaglobulinemia↗
Biomedical subjects
R A Good
Publications and source records attributed to R A Good.
Ontogeny of lymphocyte subpopulations in human fetal liver.
Lymphocytes were isolated from five fetal livers (13-17 weeks) and examined for different surface markers. Immunoglobulin M was found on 0.5-4.0% of lymphocytes. No membrane-bound surface IgD, IgA. or IgG was detected. Mouse erythrocyte rosette-forming lymphocytes ranged from 0.5 to 6.0%. Thymus-processed (T) lymphocytes, which were defined as those forming spontaneous rosettes with sheep erythrocytes, as well as lymphocytes with IgG Fc receptors, were present in a small proportion. No complement-receptor-bearing lymphocytes were found in the two cell populations of fetal liver studied. It is evident that during the ontogeny of bone-marrow-derived (B) lymphocytes IgM is the first surface immunoglobulin to appear. Receptors for the binding of mouse erythrocytes are present at the same time as surface IgM. The slight excess of mouse erythrocyte rosette-forming cells over cells having surface immunoglobulin M could mean that IgM appears later than do the receptors for the binding of mouse erythrocytes.
Animals↗
Influence of diet on survival of mice.
The longevity of mice of the (NZB X NZW)F1 (B/W) strain and the DBA/2f strain of mice is dramatically prolonged by dietary restriction. B/W mice are susceptible to, and die at an early age from, immunocomplex nephritis. Mice of the DBA/2f strain are also relatively short-lived. Restriction of caloric intake prolonged life of B/W mice more than did protein restriction. DBA/2f mice showed prolongation of life when the diet was restricted only with respect to protein. Caloric restriction alone prolonged life less in DBA/2f mice than in B/W mice. These observations show that dietary manipulations have profound effects on immunity functions, including inhibition of the development of life-shortening autoimmune disease.
Animals↗
Aplastic anemia: presence in human bone marrow of cells that suppress myelopoiesis.
Bone marrow from a patient with aplastic anemia was shown by multiple criteria to have a block in early myeloid differentiation. This block was overcome in vitro by elimination of marrow lymphocytes. Furthermore, this differentiation block was transferred in vitro to normal marrow by coculturing with the patient's marrow. We suggest that some cases of aplastic anemia may be due to an immunologically based suppression of marrow cell differentiation rather than to a defect in stem cells or their necessary inductive environment.
Adult↗
Fresh and cultured thyroid gland: survival and function after implantation.
Isogeneic or allogeneic thyroid glands were implanted into thyroidectomized recipeint rats. These grafts, either fresh or cultured, were placed in hamstring muscle pocket or under the renal capsule. Survival and function of the grafts were evaluated by: restoration of normal levels of serum thyroxine, weight gain, kidney transamidinase (a thyroxine-induced enzyme), and histological appearance of re-excised implants. A isografts, fresh and cultured, functioned well as ectopic thyroid glands, though restoration of normal serum thyroxine levels was more rapid for the fresh implants. Fresh allografts functioned transiently but then failed due to rejection. No function was detected for cultured allografts, and rejection was seen histologically. The rat thyroid allograft therefore differs from the rat parathyroid allograft, which often can function for several months despite histological evidence of rejection. Maintenance in tissue culture prior to implantation does not appear to alter the longterm immunogenicity of either organ.
Amidinotransferases↗
Linkage of gene for C2 deficiency and the major histocompatibility complex MHC in man. Family study of a further case.
Close linkage between HL-A and C2 deficiency was first reported by FU and co-workers in 1974. We present here a pedigree of a 31-year-old C2-deficient individual with clinical manifestations of Hodgkins disease. The following markers were tested: C2 levels, factor B polymorphism, blood groups, and enzyme typing. In addition to close linkage between HL-A and C2 deficiency, both parents were heterozygous for Bf (HL-A linked, electrophoretic variation of B). The two HL-A haplotypes closely linked to C2 deficiency are different: 2, W18 and W24, W18. They share, however, the SD2 antigen W18 and the LD type 7a.
Adult↗
Role of platelets in the pathogenesis of canine endotoxin shock.
Endotoxin-platelet interactions are thought to be of major importance in the response of dogs and other species to bacterial endotoxin; the mechanisms postulated are: (i) the release of vasoactive substances, (ii) the formation of occlusive platelet aggregates, and (iii) induction of intravascular coagulation. The role of platelets in canine endotoxin shock was examined in animals with thrombocytopenia induced by estrogen pretreatment (less than 10,000 platelets/mm3) and in controls. After intravenously administered endotoxin, the hemodynamic responses, mortality, and gross necropsy findings were similar in both groups. These data indicate that endotoxin-platelet interactions are not determinative in the pathogenesis of canine endotoxin shock.
Animals↗
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↗
Suppression of B-cell differentiation by leukocytes from hypogammaglobulinemic patients.
Leukocytes from patients with several forms of immunodeficiency characterized by apparently differing defects in B-lymphocyte maturation produced few or no plasmacytoid cells in vitro, and were capable of suppressing the generation of plasma cells in co-culture with cells of normal persons, in the presence of pokeweed mitogen. Such inhibition was commonly observed in cultures which included cells from patients with primary immunoglobulin deficiency, but was not seen to a significant degree in identical co-cultures of cells from normals. The suppression observed was not dependent upon mixed leukocyte culture reactivity. Both sheep erythrocyte-rosetting lymphocytes and adherent cells appeared to participate in these effects in some patients. In one patient with common variable immunodeficiency, but not in several others, removal of suppressing cells permitted the patient's remaining cells to differentiate into plasma cells in vitro. Because of the diverse syndromes in which suppression was observed, it is likely that, in at least some hypogammaglobulinemic patients, the suppression is secondary to the disease process rather than being the primary pathogenic mechanism.
Agammaglobulinemia↗
Quantitation of lymphocyte response to antigen by flow cytofluorometry.
The response of human peripheral blood lymphocytes to antigenic stimulation has been studied in vitro using flow cytofluorometry and an acridine orange (AO) staining technique for cellular deoxyribonucleic acid and ribonucleic acid (RNA). Antigen-stimulated "pyroninophillic" immunoblasts, identified by an increase in cellular content of RNA (red fluorescence with AO), were quantitated in triplicate cultures incubated up to 7 days with and without bacterial antigen. These results were similar to 14C-thymidine incorporation into identical cultures incubated in parallel. Cytofluorometric analysis showed a peak in percentage of immunoblasts after 6 days in culture, while maximum thymidine incorporation was seen on day 7. Cells from patients with depressed immune response secondary to cancer showed lower than normal antigen response by cytofluorometry. Kinetic studies revealed both a lower percentage of immunoblasts when compared to normal and a lower average per cell RNA content of the stimulated cells. AO cytofluorometry is suggested as a convenient method of simultaneously assessing lymphocyte proliferative and nonproliferative response to antigen.
Antigens, Fungal↗
Prognostic significance of lymph node histology in patients with squamous cell carcinoma of the larynx, pharynx, or oral cavity.
In a double-blind retrospective analysis, sections of lymph nodes regional to head and neck squamous cell carcinomas were microscopically examined to assess morphologically the immunologic pattern of response. Patients whose nodes showed evidence of immunologic stimulation had five-year survival rates significantly higher than those whose nodes showed no evidence of immunologic stimulation. None of the patients whose nodes showed the lymphocyte depletion pattern survived five years. The stage or histologic grade of the tumors did not influence these correlations. Metastases occurred much more frequently in patients whose nodes showed immunologic activity than in those whose did not. The data support the concept that immunologic capacities are important host defense mechanisms against malignancy. Histologic assessment of immunologic activity in regional nodes seems to be an important parameter for predicting survival.
Adult↗
Clinical immunobiology: facts and prospects.
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Histocompatibility↗
Rosette formation with mouse erythrocytes. III. Studies in patients with primary immunodeficiency and lymphoproliferative disorders.
Rosette formation with mouse erythrocytes and other cell-surface markers were examined on lymphocytes from patients with a variety of primary immunodeficiency and lymphoproliferative disorders. Mouse erythrocyte rosette-forming cells and lymphocytes with surface immunoglobulins were regularly absent in patients with Bruton type agammaglobulinaemia, immunodeficiency and thymoma syndrome and severe combined immunodeficiency disease. However, they were present in normal or low numbers in patients with common variable immunodeficiency, selective IgA deficiency and ataxis telangiectasia. Lymphocytes from patients with acute lymphoblastic leukaemia Sezary syndrome and mycosis fungoides made no or few rosettes with mouse erythrocytes. Increased numbers of mouse erythrocyte rosette-forming cells were present in patients with chronic lymphocytic leukaemia and Waldenstrom's macroglobulinaemia. The significance of the mouse erythrocyte rosette as a B-cell marker in the analysis of primary immunodeficiency and lymphoproliferative disorders is discussed.
Agammaglobulinemia↗
Rosette-formation with mouse erythrocytes. II. A marker for human B and non-T lymphocytes.
Peripheral blood lymphocytes from healthy control subjects were studied for spontaneous rosette-formation with mouse erythrocytes. The mean percentage of mouse erythrocyte rosette-forming cells (MRFC) in sixty-three subjects was 7.4X3.5; after neuraminidase treatment olymphocytes the mean percentage of mouse erythrocyte rosette-forming cells(NMRFC) was 17.2X5.6. Thymus cell suspensions made only occasional rosettes with mouse erythrocytes. There was no effect of neuraminidase treatment of thymocytes on mouse erythrocyte rosette-formation. Double labelling experiments with other cell surface markers confirmed this binding of mouse erythrocytes to be a B-cell characteristic. Monocytes and granulocytes do not bind mouse erythrocytes. It appears that there is a distinct receptor for the binding of mouse erythrocytes on the surface of lymphocytes carrying surface immunoglobulins; neuraminidase treatment of lymphocytes permits this binding to occur also on virtually all the non-T cells B cells plus the third population cells).
Age Factors↗
The use of cryopreserved lymphocytes for longitudinal studies of immune function and enumeration of subpopulations.
The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared using samples collected on five separate occasions from one normal donor. The day-to-day variation seen with the fresh cells was eliminated by the use of frozen cells. Thawed cells from one donor collected on one occasion but studied on five separate occasions and compared to fresh cells on the same days, showed fluctuations from day to day as well, confirming that the day-to-day variation seen is due to technical and not biological phenomena. Cryopreserved cells showed a decrease in responses to specific microbial antigens, a slight shift in the PHA dose-response curve, but no significant difference in responses to Con A or PWM. The relative proportion of lymphocyte subpopulations changed with freezing and thawing. The proportion of T cells increased slightly and the proportion of B cells decreased.
Antigens, Bacterial↗
Human anti-T-cell cytotoxic sera as an approach to dissection of immunological systems.
The initial work on the analysis and differentiation of human lymphoid cells is described. Cells from various lymphoid organs and blood were used as the antigen to prepare various antisera. These antisera were then used to define the lymphocyte populations of patients with primary and secondary immunodefiency. They are also being used to begin the analysis of the differentiation of the T-lymphocyte.
Animals↗
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↗
Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells.
(1)Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. (2) Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. (3) Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. (4) The findings suggest that Tcells, at an early stage of differentiation, are more susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. (5) It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstituting and cellular engineering without producing GVHD.
Animals↗