Neonatal tolerance to alloantigens is induced by enriched antigen-presenting cells.

Spleen and bone marrow cells from normal or Rag-1-deficient donors are equally competent in their ability to induce neonatal transplantation tolerance in semi-allogeneic hosts, and the latter are also capable of tolerizing fully allogeneic recipients. Both types of donor cells resulted in comparable levels of haemopoietic chimerism in tolerant animals. Lymphoid hyperactivity, however, was absent in animals tolerized with Rag-1-deficient cells.

An example of idiotypic mimicry.

We have evaluated the impact of transgenic immunoglobulin (TGIg) expression on endogenous antibody repertoires. The transgenic system was chosen as to allow for normal recombination of endogenous Ig genes, secretion of TGIg from early development on, and distinguishing the TGIg from endogenous Ig by several serological markers on the C and V regions of the molecules. The transgenic construct encodes a complete anti-(4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NP) antibody molecule carrying a well-defined idiotype, bearing a lambda 1 light chain and a chimeric heavy chain encoded by a human alpha 2 C region devoid of its membrane exon, and the murine B1.

The repertoire of serum IgM in normal mice is largely independent of external antigenic contact.

Antigen-free (AGF) and germ-free (GF) mice, although essentially free of serum IgG, maintain normal levels of circulating IgM. Using a quantitative immunoblot assay, we have now analyzed the repertoire of serum IgM from AGF, GF, and specific pathogen-free (SPF) BALB/c mice, on large panels of natural antigens from homologous tissues and bacteria. The reactivity profiles were very similar in the three groups of mice.

Differential sensitivity of B lymphocyte populations to IgM receptor ligation is determined by local factors.

Ligation of surface IgM on B cells responding to lipopolysaccharide (LPS) suppresses terminal differentiation and high-rate Ig secretion with no effect on proliferation. As shown here, different B cell populations show characteristic mean values of ligand concentration required for 50% inhibition, with Gaussian distributions of sensitivity to IgM receptor ligation that reflect cellular heterogeneity of 'al-or-none' inhibitions in single cells. Differential sensitivity of B cell populations to IgM ligation seems to be locally determined by the cellular environment and unrelated to the 'maturity' of the responding cells.

Abnormal T cell selection on nod thymic epithelium is sufficient to induce autoimmune manifestations in C57BL/6 athymic nude mice.

To investigate the role of primary T cell repertoire selection in the immunopathogenesis of autoimmune diseases, pure thymic epithelium (TE) from nonobese diabetic (NOD) embryos was grafted into non autoimmune prone newborn C57BL/6 athymic mice. The results show that NOD TE selects host T cell repertoires that establish autoimmunity in otherwise nondiabetic animals. Thus, such chimeras regularly show CD4 and CD8 T cell-mediated insulitis and sialitis, in contrast with syngeneic or allogeneic chimeras produced with TE from nonautoimmune strains.

Characteristic generated alterations of autoantibody patterns in idiopathic thrombocytopenic purpura.

Using a Western blot technique that allows quantitative detection of antibody reactivities to a large number of antigens, serum IgG and IgM antibody repertoires were compared in a group of 19 patients with a diagnosis of idiopathic thrombocytopenic purpura (ITP) and respective healthy controls. The results show that, irrespective of the duration of thrombocytopenia, age of the patients, and type of therapy, all ITP donors share characteristic alterations of serum antibody reactivity patterns on homologous erythrocyte and liver antigens. Multiparametric analyses of the immunoreactivity data readily segregated the groups of ITP and healthy donors.

Distinguishable patterns of connectivity in serum immunoglobulins from SLE patients and healthy individuals.

Given that normal individuals maintain significant levels of serum autoantibodies that share many characteristics with those found in association with autoimmune diseases (AID), it has been proposed that disease could result from defects in supraclonal regulation, namely deviations of normal patterns of immunoglobulin (Ig) connectivity. Using conventional methods, together with a recently developed technique to quantitatively score a variety of V-region-dependent serum IgG interactions, the authors have now compared serum Ig connectivity in a group of patients with systemic lupus erythematosus (SLE) to healthy controls. The results demonstrate the existence of V-region interactions of serum IgG and IgM in SLE patients and healthy donors, with comparable connectivity titres, diversity and average affinities (microM range), but a wider individual variation and a tendency for higher F(ab')2 directed reactivities in the group of SLE patients.

Instability of natural antibody repertoires in systemic lupus erythematosus patients, revealed by multiparametric analysis of serum antibody reactivities.

Recent views on autoimmune diseases invoke generalized but specific perturbations in antibody repertoires, rather than the clonally restricted or non-specific polyclonal alterations proposed thus far. The present experiments analyse serum antibody reactivities in 24 systemic lupus erythematosus (SLE) patients and 17 healthy controls, using a method that quantitatively scores a large number of antibody reactivities and allows for multiparametric statistical analyses. The results show global but relatively specific perturbations in SLE antibody repertoires, and identify novel disease-associated reactivity patterns.

Maternal IgG stimulates B lineage cell development in the progeny.

To examine the physiological role of maternal natural IgG antibodies on the development of B lineage cells of the progeny, we have bred homozygous muMT/muMT or heterozygous muMT/+ females to muMT/muMT or muMT/+ males, respectively. We could thus compare normal or B cell-deficient mice born from Ig-deprived (Ig-) or phenotypically normal mothers (Ig+). B cell-deficient progeny of heterozygous mothers contain no detectable serum IgA or IgM, but IgG concentrations that peak at 2 mg/ml by 7-21 days of age, decay after weaning with a half-life of 7 days, and remain detectable for 2 months after birth.

Targeted disruption of the V(H) 81X gene: influence on the B cell repertoire.

We have generated a mutant mouse in which the most D-proximal V(H) gene (V(H)81X) has been disrupted by introducing a neomycin-resistance gene into the V(H)81X exon by means of gene targeting in embryonic stem cells. The mutant mice generated are unable to express the V(H)81X gene but appear to display a normal pattern of B cell differentiation as well as normal numbers of bone marrow and peripheral B cells from fetal life all through ontogeny. They mount normal immune responses to several different antigens tested.

[History of lymphatic filariasis in Pernambuco. I. Epidemiologic and control aspects].

This paper is a review of lymphatic bancroftian filariasis in the State of Pernambuco. Brazil. It shows that reports have existed since the 1st decade of the century.

The age-associated increase in autoreactive immunoglobulins reflects a quantitative increase in specificities detectable at lower concentrations in young mice.

Serum immunoglobulins reactive with several autoantigens have been reported to increase with age. The authors have studied the reactivity of serum immunoglobulins from mice between 2 and 24 months of age with antigens present in lysates of syngeneic tissue extracts from young mice. The profile of immunoglobulin binding with the immunoblots of spleen and brain tissue increased progressively with age, showing only minor differences from mouse to mouse and, with one exception, revealing that the age-associated increase in binding of immunoglobulins occurred with antigens with the same migratory position in the immunoblots detectable, at lower concentration, in sera from young mice.

A model of the immune network with B-T cell co-operation. II--The simulation of ontogenesis.

This paper is based on a new model of the immune network which explicitly incorporates B-T cell co-operation. A major feature of this model is the simplifying assumption that inhibition by anti-TCR soluble Ig is the only possible down-regulatory influence on activated T-cells. This model is capable of coupling with antigens in both an "immune response" mode and a "tolerant" mode.

A model of the immune network with B-T cell co-operation. I--Prototypical structures and dynamics.

Hitherto, "second generation" network models of the immune system have all been restricted to B-lymphocytes and the Ig molecules they produce. These models have not so far been able to provide a convincing mechanism for the distinction between a "Central Immune System" (CIS) composed of a connected network of lymphocyte clones which couple with "self" antigens in a tolerant mode, and a "Peripheral Immune System" (PIS) composed of clones with little or no supra-clonal organization and which produce classical immune responses when interacting with "non-self" antigens. Here, we present a new network model which explicitly incorporates B-T cell co-operation.

Apical hypertrophic cardiomyopathy: a study of 14 patients and their first degree relatives.

Although apical hypertrophic cardiomyopathy is generally accepted as a form of hypertrophic cardiomyopathy, its underlying genetic factors, clinical course and complications may be different. The characteristics of 14 Brazilian patients with a diagnosis of apical hypertrophic cardiomyopathy are described. Symptoms were frequent and abnormal filling of the left ventricle by Doppler criteria was recorded in all patients.

The self-reactive antibody repertoire of normal human serum IgM is acquired in early childhood and remains conserved throughout life.

The authors have used a quantitative immunoblotting technique to analyse the antibody repertoire of IgM in cord blood and in the serum of young children, young adult males and aged males directed towards antigens in homologous tissues utilized as sources of self antigens. The reactivities of IgM with self antigens exhibited striking homogeneity and invariance among newborns. Self-reactive IgM repertoires of children, young adults and aged males were markedly conserved among individuals and comprised most of the anti-self reactivities that prevailed in neonates.

Ultrasonographic assessment of the adulticidal efficacy of repeat high-dose ivermectin in bancroftian filariasis.

Since diethylcarbamazine, the drug recommended for treatment of lymphatic filariasis, seems only partially effective against the adult worm, intense interest persists in identifying a macrofilaricidal drug for this infection. To evaluate directly in vivo the macrofilaricidal activity of repeat high-dose ivermectin, 15 men who had living adult Wuchereria bancrofti detected in the scrotal area by ultrasound were treated with 400 micrograms/kg of ivermectin at 2-week intervals for 6 months (total dose, 4.8 mg/kg).

Establishment of tissue-specific tolerance is driven by regulatory T cells selected by thymic epithelium.

Grafts of thymic epithelium (TE) rudiments restore T cell development and function in allogeneic athymic mice. These TE chimeras are specifically tolerant to grafts of peripheral tissues (e.g.

Ultrasonographic evidence of abnormal lymphatic vessels in young men with adult Wuchereria bancrofti infection in the scrotal area.

Purpose: We determined the prevalence and magnitude of dilatation of the lymphatic vessels of the spermatic cord in men infected with Wuchereria bancrofti, which is known major cause of hydrocele in the tropics.

Materials And Methods: Scrotal ultrasound was performed with a 7.5 MHz, transducer in 78 men from Recife, Brazil (endemic for filariasis) and in 15 from a nonendemic area.

Murine acariasis. II. Immunological dysfunction and evidence for chronic activation of Th-2 lymphocytes.

The authors describe the immunological profile of BALB/c mice with Mite-Associated Ulcerative Dermatitis (MAUD)-like disease, due to Myocoptes musculinus (Koch 1844) infestation. The disease probably involves allergic mechanisms and is characterized by erythematous and pruritic skin lesions, widespread hair loss, lymphadenopathy, lymphocytopenia, granulocytosis and wasting. Affected individuals had much reduced numbers of pre-B and B cells in bone marrow and B cells in blood; decreased T-cell numbers in peripheral lymphoid organs and blood; hypergammaglobulinaemia with selective increases of IgG1, IgE and IgA, and depletion on IgM and IgG3, the same isotype distribution being detected in splenic plasmocytes; qualitative modifications of the serum antibody reactivity pattern; and increased production of IL-4 with decreased IL-2 production after in vitro polyclonal stimulation of T cells.

Studies on the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae in paired samples of capillary and venous blood from Recife, Brazil.

We examined the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae (mf) and determined the effect of these parasite properties on the accuracy of blood filming and filtration methods for diagnosis of bancroftian filariasis in the endemic area of Recife, Brazil. Microfilariae in both venous and capillary blood exhibited a nocturnal periodicity pattern with a relatively high amplitude. Overall, capillary blood contained approximately 1.

Histological evidence for adulticidal effect of low doses of diethylcarbamazine in bancroftian filariasis.

The ability of diethylcarbamazine (DEC) to kill adult Wuchereria bancrofti worms was evaluated by examining lymphatic nodules formed after treatment with 4 different treatment schedules of 193 males living in the endemic area of Greater Recife, Brazil. Lymphatic nodules appeared in the spermatic cord or upper extremities in 43 of 138 microfilaraemic individuals, in 3 of 30 amicrofilaraemic patients with filarial disease manifestations, and in 1 of 25 asymptomatic amicrofilaraemic residents of the endemic area treated with DEC. Fourteen of these nodules were surgically removed 10-150 d after the start of treatment.