PubMed Health⌕ Search

Biomedical subjects

R S Krakauer

Publications and source records attributed to R S Krakauer.

34 records · Page 2Linked to original sources
PubMed1980

Suppressor cell defect in SLE: relationship to native DNA binding.

Recent evidence suggests the presence of a suppressor T cell defect in systemic lupus erythematosus. We confirm the presence of such a defect and find a strong quantitative correlation between the loss of suppressor T cell function and the activity of SLE as measured by the presence of antibodies to native DNA. In addition, the serum of patients with active SLE contains a soluble factor which when incubated with normal peripheral blood lymphocytes induces a suppressor T cell defect. These data are consistent with the suppressor cell defect being involved in the propagation and possible the pathogenesis of SLE, and suggests a positive feedback mechanism whereby a suppressor cell defect results in autoantibodies including antibody to suppressor cells.

Adult↗
PubMed1980

Suppression of polyclonal immunoglobulin biosynthesis by a soluble factor: T-cell dependent and T-cell independent mitogens.

When normal human spleen cells are pulsed with concanavalin A (Con A), a portion become suppressor cells which in co-culture can inhibit immunoglobulin synthesis by other normal spleen cells stimulated by pokeweed mitogen (PWM). One mechanism whereby these Con-A activated spleen cells suppress Ig synthesis appears to be by the secretion of a soluble suppressor factor(s) since supernatants of Con-A stimulated splenocytes also suppress the polyclonal synthesis of immunoglobulin by human spleen cells. In this study, we report that supernatants of Con-A activated spleen cells suppress the in vitro synthesis of IgG, IgM and IgA by human spleen cells cultured with PWM. Our results indicate that the soluble suppressor factor(s) blocks an early stage in the differentiation of B lymphocytes into plasma cells without affecting the synthesis and secretion of immunoglobulin by more mature lymphocytes which appear to be irreversibly committed toward the pathway of synthesizing immunoglobulin. In addition, we studied the ability of normal human spleen cells to synthesize polyclonal immunoglobulin when cultured with either the T-cell dependent PWM or T-cell independent mitogens lipopolysaccharide (LPS) and Nocardia. Our results demonstrate that normal human splenic mononuclear cells cultured with either Nocardia, LPS or PWM are significantly stimulated to synthesize polyclonal IgG, IgM and IgA. Furthermore, supernatants of Con-A activated human spleen cells suppressed the polyclonal synthesis of these three antibody classes by human spleen cells responding to either T-cell dependent or independent mitogens.

Cell Survival↗
PubMed1979

A quantitative assay for low levels of IgM by solid-phase immunofluorescence.

A quantitative immunofluorescent assay capable of detecting between 15 and 1450 ng of IgM on a strictly linear standard curve has been developed. The assay system is unique in that in vitro biosynthesized polyclonal IgM in culture supernatants can be quantitated with a minimal quantity of supernatant. Interference created by lectins and bead-surface interactions have been analyzed. This easily operated assay has been validated and is reliable. A very important feature of the system is the considerable cost reduction in comparsion with radiometric techniques.

Antibodies, Anti-Idiotypic↗
PubMed1978

Loss of suppressor T cells in the pathogenesis of the autoimmunity of NZB/W mice.

Loss of suppressor T cells was demonstrated in NZB/W mice, an animal model of autoimmunity. As NZB/W mice matured they lost splenic T cells that could be activated by concanavalin A (Con A) to become suppressor cells and lost the ability to produce the regulator of humoral immune responses, soluble immune response suppressor (SIRS). However, NZB/W spleen cells retained the capacity to respond to suppressor signals from Con A pulsed normal spleen cells. Thrice weekly administration of SIRS containing supernatants of Con A pulsed normal spleen cells to young NZB/W mice lead to a striking reduction in the manifestations of autoimmunity.

Aging↗
PubMed1978

Disorders of suppressor immunoregulatory cells in the pathogenesis of immunodeficiency and autoimmunity.

A series of suppressor cell systems regulate virtually all immunologic processes. Disorders of these systems have been identified in association with a number of diseases. An abnormal number of activated suppressor T-cells have been seen in some patients with common variable hypogammaglobulinemia and in some with selective IgA deficiency. Suppressor T-cells that inhibit immunoglobulin synthesis also develop in an animal model of immunodeficiency, the agammaglobulinemia of the bursectomized bird. Non-T-cell suppressor cells are a pathogenic factor in the humoral immunodeficiency associated with multiple myeloma. At the other end of the spectrum of immunologic response, a reduction in functional activity of suppressor T-cells has been implicated in the pathogenesis of autoimmune diseases. The disorders of suppressor cells that have been shown in immunodeficiency and autoimmunity are important when developing rational strategies for prevention and therapy of these immunologic disorders.

Agammaglobulinemia↗
PubMed1977

Prevention of autoimmunity in experimental lupus erythematosus by soluble immune response suppressor.

Young NZB/W mice, treated with injections of soluble immune response suppressor (SIRS)(supernatant from mouse spleen cells exposed to concanavalin A), showed decreased immunoglobulin levels, less antibody to cell nuclei, less proteinuria, and less renal pathology as compared with NZB/W mice receiving a control preparation. Thus, SIRS administration beginning at an early age appears to be an effective therapy of the autoimmune disease in NZB/W mice.

Agammaglobulinemia↗
PubMed1977

Hypogammaglobulinemia in experimental myeloma: the role of suppressor factors from mononuclear phagocytes.

We have investigated the pathogenesis of the polyclonal hypogammaglobulinemia associated with BALB/c plasmacytomas TEPC-183 and SPQC-11 to gain insight into the hypogammaglobulinemia observed in human myeloma. With pokeweed mitogen-driven IgM biosynthesis by mouse splenocytes as the indicator system for suppression, we found that a protein extract of asscites cells obtained from these tumor-bearing animals could suppress immunoglobulin production, whereas like extracts from a non-suppressing plasmacytoma, modified RPC-5, caused no suppression in vitro. Extracts of tumor ascites depleted of mononuclear phagocytes by iron carbonyl treatment showed little suppressor activity. The active extract was not cytotoxic and contained no mycoplasma or common murine viruses. Furthermore, the active suppressor factor appears to be a low m.w. protein that is not affected by treatment with ribonuclease. These results and others are consistent with the idea that the hypogammaglobulinemia of myeloma is due to the formation of immunoregulatory macrophage-like cells which synthesize a suppressor substance.

Agammaglobulinemia↗
PubMed1976

Loss of suppressor T cells in adult NZB/NZW mice.

We have investigated suppressor T-cell activity in female NZB/NZW F1 mice using PWM-driven IgM biosynthesis in vitro as an indicator system. In initial we studied we observed that spleen cells from normal mice (BALB/c, C57BL/6), as well as from young (4 wk) and adult (18 wk) NZB/NZW mice, cultured in the presence of PWM synthesize 860 +/- 120 ng IgM/10(6) cells/7 days. However, when Con A (at 2 mug/ml) was added directly to the cultures (along with PWM), cells obtained from adult normal mice and young NZB/NZW mice showed a 94% suppression of IgM synthesis, whereas cells obtained from adult NZB/NZW mice were suppressed significantly less. To analyze these findings we studied the effect of Con A-induced suppressor cells (cells cultured with Con A for 24 h and washed free of Con A) on PWM-driven IgM biosynthesis. Spleen cells obtained from normal mice cultured in the presence of Con A-pulsed cells obtained from normal mice and young NZB/NZW mice showed an 83-88% suppression of PWM-driven IgM synthesis. Similarly, supernates obtained from Con A-pulsed cells of normal mice or of young NZB/NZW mice suppressed PWM-driven IgM synthesis. This suppression by Con A-pulsed cells and their supernates required T cells since T-cell fractions but not B-cell fractions eluted from anti-Fab Sephadex columns mediated suppression of co-cultured normal cells; in addition, Con A-pulsed cells treated with anti-theta and complement do not mediate suppression. These studies of Con A-induced suppressor cell activity in normal mice and young NZB/NZW mice contrast with studies of Con A-induced suppressor cell activity in adult NZB/NZW mice. We found that adult NZB/NZW Con A-pulsed cells and supernates obtained from the Con A-pulse cells had vastly decreased suppressor potential; in this case the Con A-pulse cells and supernatant fluids derived from such cells did not suppress PWM-driven IgM synthesis by normal cells. Finally, whereas spleen cells from young and adult NZB/NZW mice differ in their suppressor cell potential, cells from both sources could respond equally to suppressor signals in that Con A-pulsed normal cells or supernates derived from such cells caused equivalent suppression of PWM-driven IgM synthesis by young and adult NZB/NZW cells. These observations allow us to conclude that NZB/NZW mice lose suppressor T-cell activity as they age.

Age Factors↗
PubMed1971

Lymphocyte stimulation: selective destruction of cells during blastogenic response to transplantation antigens.

The blastogenic response of human lymphoid cells toward any individual's transplantation antigens can be deleted by the addition of tritiated thymidine of high specific activity during the incubation of the lymphoid cells in mixed leukocyte culture. After the immunocompetent clones which responded to histocompatibility antigens had been destroyed, the remaining population still retained its capacity to respond to unrelated antigens, including other transplantation antigens.

Antibody-Producing Cells↗