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Biomedical subjects

R M Blaese

Publications and source records attributed to R M Blaese.

At least 163 records · Page 9Linked to original sources
PubMed1981

Spontaneous cytotoxicity by human peripheral blood monocytes: inhibition by monosaccharides and oligosaccharides.

The mechanism by which nonimmune cytotoxic effector cells recognize "foreign" targets for cytotoxic attack was investigated utilizing a model system in which cultured human monocytes become cytotoxic to a broad variety of xenogeneic erythrocyte target cells. Such spontaneously cytotoxic human monocytes lyse targets such as chicken (CRBC), horse (HRBC), and rat (RRBC) erythrocytes rapidly and without the addition of exogeneous lectin or antibody. It was found that a variety of simple sugars were capable of blocking the expression of cytotoxicity by precultured human monocytes, and that different oligosaccharides blocked the killing of different targets. For example, cellobiose, a beta 1-4 dimer of D (+) glucose, blocked, CRBC and HRBC lysis in vitro, but had no effect on RRBC lysis. Arabinogalactan (a complex polysaccharide with a galactose beta 1-3 galactose backbone and galactose beta 1-6 galactose side chains with terminal arabinoses), however, blocked HRBC killing, but exhibited only minor inhibition of CRBC killing. Other aspects of cell-mediated function, including lymphocyte transformation to PHA, cell viability as assessed by trypan blue exclusion, monocyte phagocytosis of opsonized CRBC's, and PHA-induced cellular cytotoxicity of CRBC targets, were essentially intact in the presence of identical concentrations of oligosaccharides. Such target-specific inhibition is consistent with the hypothesis that cytotoxic human monocytes recognize various targets through surface receptors which interact with specific monosacchardies, disaccharide, and oligosaccharide sequences present on the target surface.

Animals↗
PubMed1981

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes.

The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [3H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells.

Adult↗
PubMed1981

Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. II. Characterization of a soluble suppressor of B cell immunoglobulin production.

Human peripheral blood mononuclear cells (PBMC) activated with the mitogenic lectin concanavalin A (Con A) elaborate a soluble immune suppressor supernatant (SISS) that contains at least 2 distinct suppressor factors. One of these, SISS-B, inhibits polyclonal B cell immunoglobulin production whereas the other, SISS-T, suppresses T cell proliferation to both mitogens and antigens. The latter mediator is discussed in the companion paper. Characteristics of the human soluble suppressor of B cell immunoglobulin production (SISS-B) include: 1) inhibition by a noncytotoxic mechanism, 2) loss of activity in the presence of the monosaccharide L-rhamnose, 3) appearance within 8 to 16 hr after the addition of Con A, 4) elaboration by cells irradiated with 500 or 2000 rads, 5) production by highly purified T cells, 6) stability at pH 2.5 but instability at 56 degrees C, and 7) m.w. of 60 to 80,000. These data indicate that after Con A activation, selected T cells not only become potent suppressor cells, but also generate a soluble saccharide-specific factor(s) that inhibits polyclonal immunoglobulin production by human B cells.

Acetylglucosamine↗
PubMed1981

Reconstitution of normal megakaryocytopoiesis and immunologic functions in Wiskott-Aldrich syndrome by marrow transplantation following myeloablation and immunosuppression with busulfan and cyclophosphamide.

Three patients with Wiskott-Aldrich syndrome received transplants of marrow from their HLA-A, B, C, D identical siblings after myeloablation with busulfan, 2 mg/kg/day x 4 days, followed by immunosuppression with cyclophosphamide, 50 mg/kg/day x 4. Sustained engraftment of lymphoid and hematopoietic elements was documented in each case. Platelet counts in excess of 100,000/cu mm were restored 20--50 days posttransplant and remain in the normal range 6--12 mo later. Platelets exhibit normal size and in vitro aggregation. The patients produce isoagglutinins and antibodies to other polysaccharides. The use of busulfan in moderate dosages as a myeloablative agent, coupled with cyclophosphamide, may offer an improved alternative to the use of lethal total body irradiation as a preparative regimen for complete correction of Wiskott-Aldrich syndrome by marrow transplantation.

Bone Marrow Transplantation↗
PubMed1981

Ontogeny of humoral immune function in normal chickens: a comparison of immunoglobulin-secreting cells in bone marrow, spleen, lungs and intestine.

A reverse haemolytic plaque was employed to study the ontogeny of immunoglobulin (Ig) secreting cells of either IgG, IgA, or IgM class in normal chickens. After hatching, IgM-secreting cells were detectable in the spleen by 3 days of age whereas IgG- and IgA-secreting cells were first noted at 6 days. Adult levels of Ig-secreting cells of all three classes were attained by 31 days of age in bone marrow and two separate lymphoid populations (lamina propria and intraepithelial lymphocytes). By contrast, adult levels of Ig-secreting cells were not obtained in either the spleen or the lungs until after 50 days of age. In the case of the spleen, the delay in attainment of adult levels of total Ig-secreting cells reflected the smaller spleen size in immature birds, whereas the percentages of cells secreting Ig of each class were in the adult range by 31 days. By contrast, the numbers of cells recovered from the lungs of 50-day-old chickens were near the adult range, while the percentages of cells secreting either IgG, IgA, or IgM were much fewer than those seen in the lungs of adult chickens. These data indicate that the lungs of normal chickens are populated more slowly with Ig-secreting cells than either the bone marrow, spleen, or intestine. At all ages studied, greater numbers of Ig-secreting cells, particularly of the IgG and IgM classes, were recovered from the bone marrow and spleen as compared to the lungs and intestine. Since only a portion of the total bone marrow population was studied, these data include that the bone marrow may be a major site of Ig-secreting cells in chickens beginning shortly after hatching.

Aging↗
PubMed1980

X-linked hypogammaglobulinemia and isolated growth hormone deficiency.

We undertook clinical, immunologic, and endocrinologic studies of a family in which two brothers and their two maternal uncles had a similar disorder characterized by hypogammaglobulinemia and isolated growth hormone deficiency. Recurrent sinopulmonary infections were a prominent feature in two patients. All patients had short stature and retarded bone age during childhood, and the adults had delayed onset of puberty. The immunodeficiency was characterized by absent specific antibody production in vivo and impaired immunoglobulin production in vitro. Three of the four patients lacked circulating B lymphocytes, even though tonsils were present in those patients. All patients had deficient growth hormone responses to insulin and arginine or levodopa. These patients have an X-linked recessive disorder, but their immunodeficiency differs from the X-linked immune disorders in the World Health Organization classification; their X-linked pattern of growth hormone deficiency, without other endocrine abnormality, is also unique.

Adolescent↗
PubMed1980

Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome is an X-linked immunodeficiency disorder consisting of the triad of frequent infections, eczema, and profound thrombocytopenia. We evaluated the effects of splenectomy on hemostatic improvement and subsequent clinical course in 16 patients with the Wiskott-Aldrich syndrome. All 16 had an increase in platelet counts to at least 100,000 per cubic millimeter after splenectomy, with the mean increasing from 19,900 per cubic millimeter preoperatively to 262,700 per cubic millimeter after splenectomy. In addition, platelet size, which is characteristically small in this disease, also became normal. Survival after splenectomy correlated with the prophylactic use of antibiotics. Five of seven patients not taking prophylactic antibiotics died of sepis within 33 months of surgery. The mean survival of the nine patients maintained with prophylactic antibiotics, however, was at least 91.4 months, with six of these patients still alive an average of 11.0 years or more after splenectomy. Thus, splenectomy is a useful therapy for a major cause of morbidity and mortality in this complex syndrome.

Adolescent↗
PubMed1980

B cell differentiation and immunoregulatory T cell function in human cord blood lymphocytes.

The functional maturity of T and B lymphocyte populations from human newborns was evaluated using a reverse hemolytic plaque assay to detect immunoglobulin-secreting cells generated in in vitro cultures stimulated with pokeweed mitogen (PWM), a T cell-dependent polyclonal activator, and the Epstein-Barr virus (EBV), a T cell-independent B cell activator. Cord blood lymphocytes failed to produce immunoglobulin in response to PWM, but did respond with immunoglobulin synthesis to stimulation with EBV. Co-culture experiments demonstrated that cord blood T cells would inhibit immunoglobulin production by adult cells stimulated with PWM, but not with EBV. Cord blood T cells did suppress immunoglobulin production by cord blood B cells when stimulated with a mixture of EBV and PWM, indicating that cord blood, in contrast to adult blood, contains a population of suppressor T cell precursors that are easily activated by PWM. Irradiation of the cord blood T cells with 2,000 rad eliminated the suppressor activity and revealed normal helper function for immunoglobulin (Ig) G, A, and M when these T cells were co-cultured with adult B cells. Cord blood B cells co-cultured with adult T cells or irradiated cord blood T cells did produce immunoglobulin in response to PWM, but the response was significantly lower than that of adult B cells, and only IgM was produced in these cultures. These studies demonstrate that both the T and B cells of the human newborn have significant functional differences compared with the functions of T and B lymphocyte populations in adults.

Antibody Formation↗
PubMed1980

Evidence that specific oligosaccharides block early events necessary for the expression of antigen-specific proliferation by human lymphocytes.

We have previously shown that monosaccharides and disaccharides will block the expression of spontneous monocyte-mediated cytotoxicity. Our data were consistent with the hypothesis that human mononuclear cells express lectin-like receptors that are capable of binding to a variety sugar moieties found on target cell membranes. In this communication, we will present evidence that monosaccharides and disaccharides are also capable of blocking the expression of T cell reactivity as measured by an in vitro antigen-specific proliferative assay. The majority of sugars that blocked monocyte-mediated cytotoxicity had no effect on antigen-specific proliferation. Those sugars that did suppress antigen-induced proliferation had no effect on PHA-induced proliferation. Furthermore, some of these sugars only inhibited if they were added at the initiation of the assay; they failed to inhibit if added 24 hr after the initiation of the assay. Antigen-pulsing experiments suggested that these sugars did not block antigen uptake by human monocytes. These data suggest that a variety of cellular interactions may be mediated by receptors with specificity for simple sugars. The ability to block these naturally occurring lectins specifically both in vitro and in vivo may prove to be a powerful tool for dissecting out various forms of cellular recognition and collaboration.

Acetylgalactosamine↗
PubMed1979

MICC cytotoxic effector function of human T lymphocyte subpopulations bearing Fc-receptors for IgG and IgM.

Purified subpopulations of human T lymphocytes bearing Fc-IgG and Fc-IgM receptors were studied for their ability to mediate mitogen (PHA) induced cellular cytotoxicity (MICC) to chicken erythrocyte (CRBC) and DBA/Mastocytoma P815Y tumour cell targets. There were marked differences in the ability of the Fc-IgG receptor-bearing T cell (T gamma) and the Fc-IgM (T mu) to mediating MICC to CRBC and P815Y target cells. T gamma cells were very efficient killers of CRBC and T mu cells had no cytotoxic activity to CRBC. On the other hand, both the T gamma and T mu subpopulations were able to mediate MICC to P815Y tumour cell targets.

Cytotoxicity, Immunologic↗
PubMed1979

A receptor for IgA on human T lymphocytes.

Receptors for IgA antibody-antigen complexes were demonstrated on 2 to 18% (mean 6.7%) of human peripheral blood T cells. The proportion of cells bearing detectable IgA receptors was low in freshly prepared T cells and increased in number after 18 to 24 hr of culture similar to the time course of appearance of the Tmu receptor. These T receptors were shown to be distinctly different from Fc-IgM and Fc-IgG receptors on T cells by blocking studies with purified IgA, IgG, and IgM.

Animals↗