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Rationale for bone marrow transplantation in the treatment of autoimmune diseases.

Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevent … lls were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, …

On a regulatory gene controlling the expression of the murine lambda1 light chain.

We describe here two alleles, an allele of the lambda1 locus present in the SJL strain (rlambda1lo) and an allele of the lambda1 locus present in the BALB/c strain (rlambda1 +), of a regulatory gene locus which specifically influences the expression of the mouse lambda1 light chain structural gene. The rlambda1 regulatory gene is not linked to either the major histocompatibility complex or to the heavy-chain allogroup but appears to be linked to the lambda1 structural gene locus. In the homozygous state, the present of the rlambda1lo allele results in a 50-fold reduction in the number of lambd…

A case-control study of HLA alleles in Brazilian patients with Melkersson-Rosenthal syndrome.

Melkersson-Rosenthal syndrome (MRS) is a neuromucocutaneous disease that manifests by the triad of recurrent orofacial edema (frequently as cheilitis granulomatosa), relapsing facial paralysis and plicated tongue. The cause of MRS remains unknown, but genetic predisposal and a relationship with inflammatory bowel disease are suspected. The objective of this research was to compare the frequency of class I and II HLA alleles in patients with a confirmed diagnosis of MRS with those of a healthy control group. We conduct a case-control study and typed of HLA A, B, C, DR, and DQ using molecular te

Transcutaneous immunization with a novel imiquimod nanoemulsion induces superior T cell responses and virus protection.

BACKGROUND: Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses. OBJECTIVE: Therefore we aimed

Evidence for a Graves' disease susceptibility locus at chromosome Xp11 in a United Kingdom population.

Graves' disease (GD), which has a strong female preponderance (female/male ratio, >5:1), is inherited as a complex genetic trait. Loci for GD have started to be defined using genome-wide approaches for genetic linkage. To date, 3 loci have been confirmed in at least 2 cohorts of GD patients, the strongest effect being at the cytotoxic T lymphocyte antigen-4 (CTLA-4) locus on chromosome 2q33 in our population. Two other loci for GD have recently been proposed, but not confirmed, on chromosomes Xq21 (GD3) and 14q31 (GD1). We studied a cohort of 75 sibling pairs with GD from the United Kingdom fo

Features of the two gene pairs RD-SKI2W and DOM3Z-RP1 located between complement component genes factor B and C4 at the MHC class III region.

Located at the 30 kb genomic region between complement factor B and component C4 are four ubiquitously expressed genes RD, SKI2W, DOM3Z and RP1. Besides RP1, the protein products of the other three genes each has highly conserved homologues or related proteins in lower eukaryotes, contains leucine zipper motifs for protein interaction, and plays important roles related to RNA metabolism. RD is a subunit of the negative transcription elongation factor, critical for the regulation of gene expression. It has an RNA recognition motif and 24 copies of Arg-Asp (RD) repeats. Ski2w is a nucleolar and

Multifunctional Roles of the N-Terminal Region of HIV-1SF2Nef Are Mediated by Three Independent Protein Interaction Sites.

HIV-1 Nef promotes virus spread and disease progression by altering host cell transport and signaling processes through interaction with multiple host cell proteins. The N-terminal region in HIV-1 Nef encompassing residues 12 to 39 has been implicated in many Nef activities, including disruption of CD4 T lymphocyte polarization and homing to lymph nodes, antagonism of SERINC5 restriction to virion infectivity, downregulation of cell surface CD4 and major histocompatibility complex class I (MHC-I), release of Nef-containing extracellular vesicles, and phosphorylation of Nef by recruitment of th…

From Chickens to Humans: The Importance of Peptide Repertoires for MHC Class I Alleles.

In humans, killer immunoglobulin-like receptors (KIRs), expressed on natural killer (NK) and thymus-derived (T) cells, and their ligands, primarily the classical class I molecules of the major histocompatibility complex (MHC) expressed on nearly all cells, are both polymorphic. The variation of this receptor-ligand interaction, based on which alleles have been inherited, is known to play crucial roles in resistance to infectious disease, autoimmunity, and reproduction in humans. However, not all the variation in response is inherited, since KIR binding can be affected by a portion of the pepti…

In vitro responses of chicken macrophage-like monocytes following exposure to pathogenic and non-pathogenic E. coli ghosts loaded with a rational design of conserved genetic materials of influenza and Newcastle disease viruses.

Avian influenza virus (AIV) and Newcastle disease virus (NDV) are two important viral diseases in the poultry industry. Therefore, new disea … ne expression profile of important pro-inflammatory cytokines, a chemokine, a transcription factor, major histocompatibility complexes, and the viability of the chicken macrophage-like monocyte cells (CMM). Our genetic construct contained the external domain of matrix protein 2 and nucleoprotein gene of AIV, and immunodominant epitopes of fusion and hemagglutinin-neuraminidase pr …

Quantitating the magnitude of the lymphocytic choriomeningitis virus-specific CD8 T-cell response: it is even bigger than we thought.

Measuring the magnitudes and specificities of antiviral CD8 T-cell responses is critical for understanding the dynamics and regulation of ad … much as 95%, of the CD8 T-cell pool. Moreover, the response targeted a very broad array of peptide major histocompatibility complexes (MHCs), even though we examined epitopes derived from only two of the four proteins encoded by the LCMV genome and C57BL/6 mice only have two MHC class I alleles. These data illustrate the potential enormity, specificity, and breadth of CD8 T-cell …

A ruthenium (III) polyaminocarboxylate complex, a novel nitric oxide scavenger, enhances graft survival and decreases nitrosylated heme protein in models of acute and delayed cardiac transplant rejection.

Nitric oxide (NO) derived from the up-regulation of inducible NO synthase (iNOS) is believed to play an important role in organ rejection. In experimental models of acute cardiac transplant rejection (i.e., without immunosuppression), treatment using NOS inhibitors to prevent acute rejection have yielded conflicting results. This is most likely due to potential inhibition of constitutive NOS. Accordingly, agents that trap NO directly may have some advantage. In the current study, we evaluated the actions of a ruthenium-based NO scavenger, AMD6221, to inhibit the nitrosylation of myocardial pro

Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration.

Transplantation of allogeneic Schwann cells (SC) would make it feasible to reconstruct immediately peripheral nerve defects, compared to usi … ation into the conduit, axonal regeneration, the state of SC differentiation, and the expression of major histocompatibility complexes (MHC) I and II, as well as to quantify macrophage and B- and T-lymphocyte infiltration. Allogeneic SC were rejected by 6 weeks, whereas syngeneic SC could still be identified. Allogeneic and syngeneic SC equally enhanced the axonal regeneration di …

Genetic factors and risk of agranulocytosis from metamizol.

The role of genetic factors in the pathogenesis of agranulocytosis was investigated in agranulocytosis patients by phenotyping for N-acetyltransferase and glucose-6-phosphate polymorphism; by typing for gene products of the major histocompatability complex, ABO- and RH-blood groups, and haemoglobins; and by performing cytogenetic analysis of chromosome aberrations. Nine persons were identified as agranulocytosis cases in the period from 1982 to 1987 among the population of Sofia. They were contacted again 10 years after recovery from the disease. Five of them were associated with metamizol (di

CAR-T-Cell-Based Cancer Immunotherapies: Potentials, Limitations, and Future Prospects.

Cancer encompasses various elements occurring at the cellular and genetic levels, necessitating an immunotherapy capable of efficiently addressing both aspects. T cells can combat cancer cells by specifically recognizing antigens on them. This innate capability of T cells has been used to develop cellular immunotherapies, but most of them can only target antigens through major histocompatibility complexes (MHCs). New gene-editing techniques such as clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-cas9) can precisely edit the DNA sequences. CRISPR-c…

Transcription factor motif enrichment in whole transcriptome analysis identifies STAT4 and BCL6 as the most prominent binding motif in systemic juvenile idiopathic arthritis.

BACKGROUND: The term systemic juvenile idiopathic arthritis (sJIA) describes an autoinflammatory condition characterized by arthritis and severe systemic inflammation, which in later stages can transform into interleukin (IL)-17-driven autoimmune arthritis. IL-1 antagonists have been used with good efficacy in the early stages of sJIA. METHODS: A whole transcriptome analysis of peripheral blood RNA samples was performed in six patients with sJIA and active systemic disease, before initiating treatment with the IL-1β receptor antagonist anakinra, and after induction of inactive disease, compar

Transcriptomic and functional pathways analysis of ascorbate-induced cytotoxicity and resistance of Burkitt lymphoma.

Ascorbate is a pro-oxidant that generates hydrogen peroxide-dependent cytotoxity in cancer cells without adversely affecting normal cells. To determine the mechanistic basis for this phenotype, we selected Burkitt lymphoma cells resistant to ascorbate (JLPR cells) and their ascorbate-sensitive parental cells (JLPS cells). Compared with JLPS cells, the increased glucose uptake in JLPR cells (with upregulated glucose transporters, increased antioxidant enzyme activity, and altered cell cycling) conferred ascorbate-induced cytotoxicity and resistance. Transcriptomic profiles and function pathway

Nickel allergy in mice: enhanced sensitization capacity of nickel at higher oxidation states.

Attempts to induce contact hypersensitivity to nickel in mice using, e.g., Ni(II)Cl2 often failed. Here, we report that sensitization was achieved by injecting Ni(II)Cl2 in combination with either CFA or an irritant, such as SDS and PMA, or IL-12, or by administering nickel at higher oxidation states, i.e., Ni(III) and Ni(IV). Although Ni(II), given alone, was ineffective in T cell priming, it sufficed for eliciting recall responses in vivo and in vitro, suggesting that Ni(II) is able to provide an effective signal 1 for T cell activation, but is unable to provide an adequate signal 2 for prim

[The onset mechanism of experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein].

In order to analyze the onset mechanism of experimental autoimmune uveoretinitis (EAU), two experimental models were used; one was EAU induc … ctivated. Activation begins when the T lymphocyte recognizes the peptide for the epitope bound to a major histocompatibility complex (MHC) molecule in the antigen-presenting cell by way of the T-cell receptor (TCR). In EAU, ten peptide residues p1182-1191 of the IRBP amino acid sequence, were revealed to be sufficiently capable of lymphocyte activation for EAU, and it was also sh …

Аутоиммунное заболевание: генетическая восприимчивость, экологические факторы и регулирование иммунной дисдукции. Где мы можем развивать терапию?

Аутоиммунные заболевания представляют собой разнообразную группу хронических расстройств, характеризующихся неадекватной иммунной реакцией на самоантигены, приводящей к стойкому воспалению и разрушению тканей. Эти условия, затрагивающие примерно 7-10% населения мира, включают как системные, так и специфические для органов организмы, такие, как системная волчанка (SLE), ревматоидный артрит (RA), диабет типа 1 (T1D) и множественный склероз (MS). Несмотря на их клиническую неоднородность, аутоиммунные заболевания имеют общую этиологическую структуру, которая включает конвергенцию генетической пре

Совпадение в аннотации оригинала
Autoimmune diseases are a diverse group of chronic disorders characterized by inappropriate immune responses against self-antigens, resultin … nome-wide association studies (GWAS) have identified hundreds of risk loci, most notably within the major histocompatibility complex (MHC), and highlighted the role of non-HLA genes regulating cytokine signaling, antigen presentation, and T cell tolerance. The majority of disease-associated variants lie in non-coding regulatory elements, suggesting that transcriptional dysregulat …