Kinetics of the appearance of HLA-DR antigens on human alloactivated T lymphocytes and the demonstration of new antigenic determinants

By studying serologically the appearance of HLA-DR determinants on T lymphocytes activated by a mixed lymphocyte culture, we have been able to demonstrate the existence of a new class of antigenic determinants distinct from classical HLA-DR antigens. Indeed, some monospecific anti-DR sera were cytotoxic from some alloactivated T cells, though not directed against their HLA-DR specificity. The absorption of these anti-sera on B lymphocytes bearing the HLA-DR antigen against which they were directed, did not remove their reactivity on alloactivated T lymphocytes. The absorption of the same anti-sera on activated T lymphocytes did not affect their anti-DR reactivity. This study shows the existence of new antigenic determinants expressed by T lymphocytes during their activation: alloactivated T lymphocyte antigens (AATL).     

Effects in man of a total adrenal cortical extract on delayed immunity and lymphocyte sub-populations]

After a 10 day treatment with total adreno-cortical extract, administered to 11 subjects, the following results were obtained: increase of delayed cutaneous responses to various antigens, increase in the number of null lymphocytes, decrease in the number of B lymphocytes. These changes did not occur in 16 control patients who were not treated.     

Abstossung von Tumoren unter Einwirkung von anorganischem Diphosphat

Summary Eels with dermal tumors, consisting mainly of undifferentiated epidermal cells, have been treated with inorganic diphosphate. Depending on concentration of the diphosphate used, the tumors show either an increased number of mucous cells or they are repelled. In the adjacent tissue of the cutis, during these processes, a great number of lymphocytes and macrophages are found. Three possibilities are offered to explain these facts, the most important of which is that the diphosphate increases the ability of the tumor cells to redifferentiate. Consequently, formation of tumor specific antigens is induced, as a result of which the tumor is destroyed by an immunbiological reaction.     

Decrease of mast cells in regional lymph nodes in response to allogeneic antigens and syngeneic tumor antigens

Summary The absolute number of mast cells in regional lymph nodes decreases on the 5th day after stimulation by allogeneic lymphocytes and semisyngeneic leukaemic cells, despite the enlargement of stimulated lymph nodes. It is postulated that the reaction of lymphatic mast cells could be a sensitive test for tissue incompatibility, and probably also for the presence of tumor associated antigens.     

Production of monoclonal anti-Schistosoma mansoni antibodies. Preliminary study of their biological activities]

Monoclonal antibodies against Schistosoma mansoni have been produced by fusion of splenic lymphocytes from S. mansoni infected Rats and P3-X63-Ag8 BALB/c cells. In vitro and in vivo studies of the biological activities of these antibodies have led to the identification of IgE antibodies with a high reaginic activity and antibodies which in a complement dependent or eosinophil dependent system were shown to have a marked cytotoxicity for schistosomula in vitro. This methodology seems to open new perspectives for the study of antibody function in immunity against parasites as well as for the isolation of the corresponding target antigens.     

The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation

A challenging task for the adaptive immune system of vertebrates is to identify and eliminate intracellular antigens. Therefore a highly specialized antigen presentation machinery has evolved to display fragments of newly synthesized proteins to effector cells of the immune system at the cell surface. After proteasomal degradation of unwanted proteins or defective ribosome products, resulting peptides are translocated into the endoplasmic reticulum by the transporter associated with antigen processing and loaded onto major histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are transported via the secretory pathway to the cell surface where they are then inspected by cytotoxic T lymphocytes, which can trigger an immune response. This review summarizes the current view of the intracellular machinery of antigen processing and of viral immune escape mechanisms to circumvent destruction by the host. Received 4 October 2005; received after revision 19 November 2005; accepted 24 November 2005     

Repair of fundo-antral gastric fistula by homologous and heterologous fundo-antral tranplansts in adult rats]

Use of fundo-antral gastric transplants excised from Rat or guinea-pig stomach in order to repair fundo-antral fistula was well tolerated by adult Rats and compatible with a normal survival. In 90% of homologous transplantation, and 70% of heterologous transplantation, no brutal and mortal rejection of transplant was observed. The transplant did not regenerate, but its corpse was not eliminated, and remained united to the wall of the receiver's stomach, and infiltrated with lymphocytes. We explain the benignity of immunologic reaction in evoking the role of the liver which acts as a filter in sequestering a great part of antigens, and so moderating the antibody response by the spleen and lymphoid system.     

Comparative evaluation of 7 helminth antigens in the enzyme-linked immunosorbent assay (E.L.I.S.A.).

112 sera from Europeans with parasitologically proven helminthiasis were tested in the enzyme-linked immunosorbent assay (E.L.I.S.A.) against 6 crude extracts of various helminths (2 of adult worms: Dipetalonema viteae, Fasciola hepatica; 3 of eggs: Ascaris suum, Toxocara canis, Schistosoma mansoni; and of Echinococcus granulosus scolices) and against bovine hydatid fluid. Each serum was tested simultaneously at a fixed dilution of 1:160 against all antigens. Extensive cross-reactions were observed, leading to the conclusion that non-purified helminth antigens, even in combination, are of limited value for reliable serodiagnosis in E.L.I.S.A.     

The morphology of cytoplasts and karyoplasts produced by cytochalasin D.

The denucleation of L cells and human lymphocytes in suspension was carried out by incubation with cytochalasin D25 and 50 microgram/ml and with ultracentrifugation over a discontinuous Ficoll gradient. Ultrastructural examination of the separate layers confirmed the presence of the anucleate cytoplasm (cytoplasts) with intact membrane and the separated nuclei (karyoplasts).     

Comparative evaluation of 7 helminth antigens in the enzyme-linked immunosorbent assay (E.L.I.S.A.)

Summary 112 sera from Europeans with parasitologically proven helminthiasis were tested in the enzyme-linked immunosorbent assay (E.L.I.S.A.) against 6 crude extracts of various helminths (2 of adult worms:Dipetalonema viteae, Fasciola hepatica; 3 of eggs:Ascaris suum, Toxocara canis, Schistosoma mansoni; and ofEchinococcus granulosus scolices) and against bovine hydatid fluid. Each serum was tested simultaneously at a fixed dilution of 1:160 against all antigens. Extensive cross-reactions were observed, leading to the conclusion that non-purified helminth antigens, even in combination, are of limited value for reliable serodiagnosis in E.L.I.S.A.     

Studies on the relationships between biotin and the behaviour of B and T lymphocytes in the guinea-pig

Summary In biotin-deficient guinea-pigs the number of circulating neutrophils is increased; lymphocytes carrying B and T markers are decreased. Incubation with biotin increases significantly the number of lymphocytes carrying B and T markers, from biotin-deficient guinea-pigs; no increase was observed when the lymphocytes from normal guinea-pigs were incubated.     

Molecular mimicry and the role of B lymphocytes in the processing of autoantigens

The immune system has evolved several mechanisms that provide lymphocytes with the intelligence to ignore self proteins while attacking foreign pathogenic agents. Notably, B and T lymphocytes that encounter self antigen at either the inappropriate levels or affinity are usually instructed to perish or become anergized. However, the presence of autoimmune disease suggests that the induction of self tolerance is not foolproof. In fact, autoreactive cells are now found to be normal inhabitants of the B and T lymphocyte repertoire. This review examines how foreign peptides which resemble self proteins can elicit autoimmunity that is amplified to many sites on a target autoantigen. In particular, B lymphocytes initiated by foreign molecular mimics can process and present self peptides in the shaping of autoimmune T cell responses.     

A population of human lymphocytes staining for esterases

Summary A population of lymphocytes is found to stain positively for esterases. The positively staining lymphocytes are more predominant among T than B lymphocytes and are significantly increased on stimulation with PHA. Treatment with cholinestrase inhibitors reduces their number significantly.This work was supported by a grant from the Medical Research Council of Canada.     

Steady-state kinetic studies with the polysulfonate U-9843, an HIV reverse transcriptase inhibitor

The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT^* and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed RNA-directed DNA polymerase activity were carried out in order to determine if the inhibitor interacts with the template: primer or the deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics, which are based on the establishment of a rapid equilibrium between the enzyme and its substrates, proved inadequate for the analysis of the experimental data. The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming that the template:primer binds to the enzyme first, followed by the binding of the dNTP and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived which allows the calculation of all the specific forward and backward rate constants for the reactions occurring between the enzyme, its substrates and the inhibitor. The calculated rate constants are in agreement with this model and the results indicated that U-9843 acts as a noncompetitive inhibitor with respect to both the template:primer and dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase by interacting with a site distinct from the substrate binding sites. Thus, U-9843 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either an event leading up to the formation of the phosphoester bond, the formation of the ester bond itself or translocation of the enzyme relative to its template:primer following the formation of the ester bond.     

Necessity of adjuvants for inducing effective antibody response to zona pellucida antigens

Summary Rhesus monkeys evoked a vigorous antibody response to a single heteroimmunization dose of zona pellucida antigens, when these were administered along with complete Freud's adjuvant. The antisera recognized all the three major porcine zona glycoprotein families and the animals were rendered amenorrheic after such immunization. Monkeys immunized with zona without adjuvant, however, failed to show any anti-zona antibody response and had normal menstrual cycles. Zona pellucida glycoproteins are thus not effective immunogens unless administered along with a powerful adjuvant.     

Zur Immunchemie der Klebsiella-Antigene

Summary The capsular (K) and somatic (O) antigens of 72 Klebsiella-type strains were isolated and investigated with respect to their chemical composition and their serological behaviour. The K antigens were found to be acidic heteropolysaccharides carrying serological K specificity. The O antigens are lipopolysaccharides which are O group-specific.     

Attempt to alter antigenic structure of normal tissues by treatment with dimethyl-triazeno-imidazole-carboxamide in vivo

Summary The antigenic structure of normal skin and spleen cells has been investigated following in vivo treatment with the compound DIC. In experiments involving skin grafting in the normal and sensitized host, cross sensitization with a DIC-antigenic lymphoma and³H-thymidine incorporation by lymphocytes cultured with DIC-treated spleen cells, new antigens on DIC-treated tissues were not demonstrated.Research supported in part by Contract No. 74.00237.04 from C.N.R., Rome.We wish to thank Mr.C. R. Reeder of the Mammalian Genetics and Animal Production Section of NCI, NIH, Bethesda, Maryland, USA, for breeding and providing the animals, and Serpero Foundation, Milan, for support. The proficient technical assistance of Ms.C. Cattoi andD. Peroni is also acknowledged.     

Necessity of adjuvants for inducing effective antibody response to zona pellucida antigens

Rhesus monkeys evoked a vigorous antibody response to a single heteroimmunization dose of zona pellucida antigens, when these were administered along with complete Freund's adjuvant. The antisera recognized all the three major porcine zona glycoprotein families and the animals were rendered amenorrheic after such immunization. Monkeys immunized with zona without adjuvant, however, failed to show any anti-zona antibody response and had normal menstrual cycles. Zona pellucida glycoproteins are thus not effective immunogens unless administered along with a powerful adjuvant.     

Alternative pathways for MHC class I presentation: a new function for autophagy

The classical view that endogenous antigens are processed by the proteasome and loaded on MHC class I molecules in the endoplasmic reticulum, while exogenous antigens taken up by endocytosis or phagocytosis are degraded and loaded on MHC class II in lysosome-derived organelles, has evolved along with the improvement of our understanding of the cell biology of antigen-presenting cells. In recent years, evidence for alternative presentation pathways has emerged. Exogenous antigens can be processed by the proteasome and loaded on MHC class I through a pathway called cross-presentation. Moreover, endogenous antigens can be targeted to lytic organelles for presentation on MHC class II through autophagy, a highly conserved cellular process of self-eating. Recent evidence indicates that the vacuolar degradation of endogenous antigens is also beneficial for presentation on MHC class I molecules. This review focuses on how various forms of autophagy participate to presentation of these antigens on MHC class I.