Randall S. Krakauer

Immunologic enhancement of collagen accumulation in progressive systemic sclerosis (PSS)

Abstract Progressive systemic sclerosis (PSS, systemic scleroderma) is a generalized connective tissue disorder in which the involved tissues exhibit an array of fibrotic and degenerative changes including an abundant accumulation of collagen. Activated normal human lymphocytes produce factors which are capable of stimulating normal fibroblast proliferation and collagen accumulation. In this study we investigate the effects of similar factors obtained from lymphocytes of scleroderma patients as well as from those of normal individuals on fibroblast proliferation and protein synthesis. Lymphocytes from scleroderma patients when compared with normal donors were found to produce soluble factors which induced enhanced normal fibroblast synthesis of protein, particularly collagen, without inducing increased proliferation. Our findings suggest altered immunoregulation of collagen metabolism in individuals with scleroderma.

Suppressor cell function defect in idiopathic systemic lupus erythematosus

Abstract Six normals and 12 patients with idiopathic systemic lupus erythematosus (SLE) who had received no therapy other than nonsteroidal, anti-inflammatory medication were studied for suppressor cell function. In vitro immunoglobulin synthesis by normal B cells was suppressed by concanavalin A (Con A)-stimulated allogeneic normal lymphocytes, whereas Con A-stimulated lymphocytes from patients with SLE mediated significantly less suppression of normal lymphocytes. In addition, although B cells from patients with SLE synthesized less immunoglobulin in the presence of normal T cells than did normals, T cells from patients with SLE mediated significantly less allogeneic suppression of immunoglobulin synthesis by normal B lymphocytes than did T cells from normal individuals. SLE B cells are, nonetheless, sensitive to T-cell-mediated suppression. This suppressor cell defect might contribute to the pathogenesis of SLE. Several plausible causes for this defect are considered.

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.

Human splenic and peripheral blood lymphocyte response to lipopolysaccharide

Abstract In this study we investigated the mitogenic effect of lipopolysaccharide (LPS) on human splenic and peripheral blood lymphocytes. Human splenic lymphocytes were found to proliferate and synthesize IgG, IgA, and IgM in response to LPS. The sensitivity of our assay for IgA and IgG classes of immunoglobulin may account for our observation of their synthesis. Fresh human peripheral blood lymphocytes did not proliferate or synthesize immunoglobulin in response to LPS. Increasing the doses of LPS and altering the length of incubation did not affect this result. If the lymphocytes were incubated for 20 hr prior to exposure to LPS, however, both proliferation and immunoglobulin synthesis, similar in magnitude to LPS-stimulated splenic lymphocytes, were observed. These results suggest the presence of a suppressor cell which is eliminated by preincubation or the maturation of an LPS-responding population during preincubation. The former explanation appears more likely when the results of other investigations are taken into consideration.

The influence of thymic humoral factor on systemic lupus erythematosus lymphocyte function

The influence of thymic humoral factor, THF, on systemic lupus erythematosus, SLE, lymphocyte function was investigated. Increasing numbers of SLE T-cells, rosetted at 4 degrees C or 37 degrees C, were cultured with allogeneic normal B-cells and the change in IgM synthesis was assessed. Lymphocytes of some SLE patients showed improved suppression with THF when rosetted at 37 degrees C. Normal control lymphocytes did not show a net change in suppression with THF. The subgroup of SLE patients that showed improved suppression with THF in vitro might be a more appropriate group for in vivo therapeutic trials with thymic hormone, TH, than SLE patients in general.

Suppressor cells in common variable hypogammaglobulinemia with SRBC receptors and surface immunoglobulin

Abstract Common variable hypogammaglobulinemia (CVH) or adult-onset agammaglobulinemia is an acquired humoral immune deficiency characterized by low levels of circulating IgG, IgA, and usually IgM, frequent sinopulmonary infections and commonly, gastrointestinal tract infections. Although its place in the pathogenesis of this disease is unclear, a portion of patients with CVH have circulating suppressor T-lymphocytes capable of inhibiting immunoglobulin synthesis by B-lymphocytes of both the patient himself and normals with no humoral immune deficiency. In at least some situations, B-lymphocytes from such patients are capable of immunoglobulin synthesis when removed from the suppressor influences of their own T-cells. Although in mice surface antigens have been identified which are in varying degrees specific for suppressor cells, such cells have not yet been separated in humans. Although human T-lymphocytes with IgM Fc receptors have been characterized as helpers, while those with IgG Fc receptors as suppressors, there are experimental circumstances in which this division breaks down. We here describe a patient with common variable hypogammaglobulinemia with circulating suppressor cells whose unique surface characteristics enabled their physical separation.