H. H. Fudenberg

ISOLATION OF NORMAL T CELLS IN CHRONIC LYMPHATIC LEUKÆMIA

Abstract Lymphocytes from patients with chronic lymphatic leukaemia (C.L.L.) show a poor response to mitogens. Lymphocytes from these patients and from healthy patients were separated into two populations. One population, very rich in T cells, showed the same type of response for both the controls and patients. In contrast, the population poor in T cells derived from C.L.L. lymphocytes did not respond at all to mitogens. Recombination experiments indicate that the response can be restored by the addition of T cells. These findings demonstrate the presence of a normally reactive T-cell population in patients with C.L.L. It seems that the lack of responsiveness in C.L.L. is due to the dilution of normally responding cells.

Antibody to Hereditary Human Gamma-Globulin (Gm) Factor Resulting from Maternal-Fetal Incompatibility

Multiple samples of serum from a Gm(a-) female mated to a Gm(a+) male were obtained before, during, and after each of four normal uncomplicated pregnancies and tested for antibody to human gamma globulins of differing genetic types. An agglutinator for the Gm(a) factor first appeared in the mothers serum during the third trimester of the fourth pregnancy. The newborn (male) was genotypically Gm(a+), since his serum contained, in addition to maternal Gm(a-) gamma globulin, small amounts of Gm(a+) gamma globulin.

Ontogeny of cellular immunity in the human fetus: development of responses to phytohemagglutinin and to allogeneic cells.

Abstract Human fetal lymphoid cells from thymus, spleen, blood, liver, and bone marrow of 22 fetuses (5–19 weeks of fetal age) were studied for their ability to respond to phytohemagglutinin and to adult allogeneic lymphocytes by the mixed lymphocyte reaction. The earliest detectable response was that by hepatic cells in the mixed lymphocyte reaction at 7.5 weeks of fetal age. Phytohemagglutinin reactivity was initially seen in the thymus at 10 weeks, in blood at 14.5 weeks, and in spleen at 13 weeks. Mixed lymphocyte reaction reactivity was first detected in the thymus at 12.5 weeks; it appeared somewhat later in peripheral organs. Few significant responses to phytohemagglutinin were detected in bone marrow or hepatic cells, and virtually no response to allogeneic cells was found in bone marrow. All lymphoid cells studied showed stimulatory ability in the mixed lymphocyte reaction. However, spleen, blood, and marrow cells produced higher stimulation of allogeneic cells than did thymic or hepatic cells.

The incidence and antigenic specificity of antibodies against denatured human collagen in rheumatoid arthritis

Abstract Antibodies to denatured human collagen were identified in sera of rheumatoid arthritis patients. The incidence of anti-collagen antibodies was about 60% in 100 arthritis sera and about 9% in 400 age and sex-mathched control sera. Also, the titers ranged from 1:8 to 1:512 in the rheumatoid sera, compared to a maximum of 1:4 in the controls. The occurrence of anti-collagen was shown to be independent of rheumatoid factor and was shown to be primarily of the IgG class. Both α1 and α2 chains of collagen were recognized by rheumatoid anti-collagen antibodies. Assays with five sera showed that the major antigenic determinants were cyanogen bromide fragments α1CBO, 1, and α2CB3.

Peyer's patches: Morphologic studies

Abstract The aggregates of lymphoid tissue associated with the intestine represent a large fraction of the total lymphoid tissue of rabbits (1) and presumably have an important immunological function. The importance of intestinal plasma cells in the synthesis of IgA is established, but the IgA synthesizing cells seem to be diffusely scattered through the lamina propria rather than existing in the follicle-like aggregates (2). It has been suggested that the aggregates are responsible for the local production of IgG and IgM antibodies against the bacterial and food antigen present in the gut, but there has been some difficulty in experimentally substantiating this concept (3, 4). Some investigators have proposed that the gut-associated lymphoid tissues have a central function in the ontogeny of the immune response. The lymphoid system of birds is considered to consist of two components. These are ( a ) thymic-dependent lymphocytes, and ( b ) a system of plasma cells and germinal centers dependent on the bursa of Fabricius (5). Cells under thymic control are thought to be responsible for cellular immunity (6), and bursal oriented tissues for immunoglobulin synthesis (7, 8). Lymphoepithelial differentiation in both the thymus and the bursa of Fabricius are believed to be governed by mesenchymal induction (9, 10), though this has been questioned (11). Morphologic and phylogenetic studies have suggested that the rabbit equivalent of the avian bursa is a lymphoepithelial structure in the intestinal tract (12–14). The development of the appendix and Peyers patches are not dependent on the presence of the thymus (15, 16). Surgical removal of gut-associated lymphoid centers in rabbits has resulted in a condition resembling bursectomy and sublethal irradiation in birds (17, 18) suggesting that the Peyers patch may be the rabbit equivalent of the avian bursa. The division of lymphoid organs into “central” or “peripheral” categories is generally based on a number of nonimmunologic criteria among which are morphology, the stage of development at birth, and the patterns of cellular repopulation. On immunologic grounds, central organs are considered to be essential in the genesis of immune reactivity, but not to participate directly in the response. There is a paucity of information on the morphology of Peyers patches, and the evidence for their direct participation in the immune response is conflicting. The investigations reported in this paper were undertaken to provide information on the structure and ultrastructure, the histochemistry, and the cellular kinetics of rabbit Peyers patches. We have included tissues from young and mature rabbits and rabbits which had received repeated injections of antigens in the hope of disclosing differences among the groups which might shed some light on the function of the organs. In view of the specialized role proposed for the overlying epithelium, we were particularly interested in characteristics which distinguish it from the general gut epithelium. The electron microscope has also permitted a closer inspection of the anatomical relationships between the cells.

Factor VIII Detection by Hemagglutination Inhibition: Hemophilia A and von Willebrand's Disease

Factor VIII activity was detected immunologically in both the serums and plasmas of 14 normal individuals and 14 patients with hemophilia A. A hemagglutination-inhibition test with rabbit antibody to highly purified (10,000-fold) factor VIII from humans was used. Serums and plasmas from eight patients with von Willebrands disease showed little or no factor VIII activity in this test, an indication that the test may serve as a specific assay for differentiation between von Willebrands disease and hemophilia A.

The Therapeutic Uses of Transfer Factor

For many years transfer factor, the cell-free leukocytic extract capable of transferring delayed hypersensitivity reactivity, was controversial, even with respect to its very existence. Recent work, however, has clearly delineated a clinical potential for transfer factor in the treatment of some immunodeficiency diseases, and possibly also as an adjunct in the management of certain cancers.

The papain susceptibility of IgG myeloma proteins of different heavy chain subclasses

Abstract Papain-susceptibility of 50 IgG myeloma proteins was investigated. 34 per cent of the proteins proved to be papain-resistant. A definite correlation between papain-susceptibility and heavy chain subclass was found in the cases of myeloma proteins belonging to subclasses IgG2, IgG3, and IgG4, as the IgG2 and IgG4 proteins were papain-resistant, whereas the IgG3 proteins were papain-sensitive. There exists, however, a heterogeneity in the subclass IgGl.

Chemical differences of adult, fetal and hypogammaglobulinemic IgG immunoglobulins☆

Abstract Heavy and light chains of IgG molecules from pooled normal adult sera, pooled normal fetal sera, and pooled hypogammaglobulinemic sera were studied by means for starch gel electrophoresis in hypertonic urea. Differences were demonstrated among the heavy chain preparations. These data indicated that: 1. (1) The transfer of IgG molecules across the placenta has a selective nature. Not all species of material IgG pass equally well into the fetal circulation. IgG2 subclass immunoglobulins were detected in the fetal serum in only trace amounts. 2. (2) Neonatal IgG molecules are not entirely composed of molecules passively transferred from the mother. 3. (3) IgG molecules from hypogammaglobulinemic patients are less heterogeneous than those from normal people.

Stimulation of heme oxygenase in macrophages and liver by endotoxin.

In rat peritoneal macrophages, engaged in erythrophagocytosis in vitro, endotoxin stimulated heme oxygenase (HO) activity, which was additive to the substrate-mediated enzyme induction produced by the ingested erythrocyte hemoglobin. Endotoxin neither appeared to injure the erythrocytes, nor did it enhance the rate of erythrophagocytosis. In intact rats, HO activity in both parenchymal and sinusoidal cells of the liver was increased after treatment with endotoxin. It is likely that endotoxin directly stimulates HO activity, a process which may account for the reported rise in bilirubin formation in endotoxin-treated animals. The effect of endotoxin on HO may represent part of the general activation of phagocytic cells by endotoxin.