Henri Temianka Correspondence; (askenase)

This collection contains material pertaining to the life, career, and activities of Henri Temianka, violin virtuoso, conductor, music teacher, and author. Materials include correspondence, concert programs and flyers, music scores, photographs, and books.https://digitalcommons.chapman.edu/temianka_correspondence/3323/thumbnail.jp

Henri Temianka Correspondence; (askenase)

This collection contains material pertaining to the life, career, and activities of Henri Temianka, violin virtuoso, conductor, music teacher, and author. Materials include correspondence, concert programs and flyers, music scores, photographs, and books.https://digitalcommons.chapman.edu/temianka_correspondence/1107/thumbnail.jp

Functional Education of Monocytes During Infection

Tissue-infiltrating Ly6Chi monocytes play important protective roles during infection, including inflammatory cytokine secretion and pathogen killing. Here we show that during acute gastrointestinal infection with the protozoan parasite Toxoplasma gondii, recruited monocytes not only contributed to parasite control, but also regulated pathologic immune responses to commensal microbes via secretion of the lipid mediator prostaglandin E2 (PGE2). Priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic IL-12 produced by Batf3-dependent dendritic cells (DC) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals following tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function

Antibody light chains dictate the specificity of contact hypersensitivity effector cell suppression mediated by exosomes

Antibody light chains (LCs), formerly considered a waste product of immunoglobulin synthesis, are currently recognized as important players in the activation of the immune response. However, very little is known about the possible immune regulatory functions of LCs. Recently, we reported that hapten-specific LCs coat miRNA-150-carrying exosomes produced by CD8+ suppressor T cells downregulating the contact hypersensitivity (CHS) reaction in an antigen-specific manner, in mice tolerized by intravenous administration of a high dose of hapten-coupled syngeneic erythrocytes. Thus, the current studies aimed at investigating the role of hapten-specific LCs in antigen-specific, exosome-mediated suppression of CHS effector cells. Suppressor T cell-derived exosomes from tolerized B-cell-deficient µMT−/−, NKT-cell-deficient Jα18−/−, and immunoglobulin-deficient JH−/− mice were nonsuppressive, unless supplemented with LCs of specificity strictly respective to the hapten used for sensitization and CHS elicitation in mice. Thus, these observations demonstrate that B1-cell-derived LCs, coating exosomes in vivo and in vitro, actually ensure the specificity of CHS suppression. Our research findings substantially expand current understanding of the newly discovered, suppressor T cell-dependent tolerance mechanism by uncovering the function of antigen-specific LCs in exosome-mediated, cell–cell communication. This express great translational potential in designing nanocarriers for specific targeting of desired cells

Orally administered exosomes suppress mouse delayed-type hypersensitivity by delivering miRNA-150 to antigen-primed macrophage APC targeted by exosome-surface anti-peptide antibody light chains

We previously discovered suppressor T cell-derived, antigen (Ag)-specific exosomes inhibiting mouse hapten-induced contact sensitivity effector T cells by targeting antigen-presenting cells (APCs). These suppressive exosomes acted Ag-specifically due to a coating of antibody free light chains (FLC) from Ag-activated B1a cells. Current studies are aimed at determining if similar immune tolerance could be induced in cutaneous delayed-type hypersensitivity (DTH) to the protein Ag (ovalbumin, OVA). Intravenous administration of a high dose of OVA-coupled, syngeneic erythrocytes similarly induced CD3+CD8+ suppressor T cells producing suppressive, miRNA-150-carrying exosomes, also coated with B1a cell-derived, OVA-specific FLC. Simultaneously, OVA-immunized B1a cells produced an exosome subpopulation, originally coated with Ag-specific FLC, that could be rendered suppressive by in vitro association with miRNA-150. Importantly, miRNA-150-carrying exosomes from both suppressor T cells and B1a cells efficiently induced prolonged DTH suppression after single systemic administration into actively immunized mice, with the strongest effect observed after oral treatment. Current studies also showed that OVA-specific FLC on suppressive exosomes bind OVA peptides suggesting that exosome-coating FLC target APCs by binding to peptide-Ag-major histocompatibility complexes. This renders APCs capable of inhibiting DTH effector T cells. Thus, our studies describe a novel immune tolerance mechanism mediated by FLC-coated, Ag-specific, miRNA-150-carrying exosomes that act on the APC and are particularly effective after oral administration

Specialized antigen-presenting cells. Splenic-dendritic cells and peritoneal-exudate cells induced by mycobacteria activate effector T cells that are resistant to suppression

We have tested the ability of several types of trinitrophenyl (TNP)-labeled Ia+ cells to induce contact hypersensitivity (CS) after intravenous injection. Most labeled cell types (spleen cells, splenic macrophages, various types of peritoneal-exudate cells) not only fail to induce CS after this type of inoculation but, rather, activate T suppressor cells leading to specific immunological tolerance. Occasionally, some of these immunizing cells managed to bypass the T suppressor system and induced CS. In these cases the response was short-lived and could be blocked by concomitant injection of trinitrobenzelsulphonic acid (TNBS), a potent inducer of T suppressor cells. In sharp contrast to these results, TNP-labeled splenic dendritic cells and TNP-labeled peritoneal-exudate cells induced by complete Freund\u27s adjuvant had the following distinctive features: (a) They were always able to sensitize when injected intravenously, and the degree of sensitization they produced was roughly equivalent to that achieved by cutaneous application of picryl chloride, the chemically reactive form of TNP. (b) The response they elicited was long lived (i.e., lasted for \u3e3 wk). (c) Their sensitizing capacity could not be blocked by the concomitant injection of TNBS. (d) They elicited a response that could be adoptively transferred to untreated, normal recipients. These results indicate that the type of cell that first presents antigen to the immune system plays an important, even essential, role in determining the strength and duration of the subsequent immune response. In particular, the results suggest that some special antigen-presenting cells can induce a response that is relatively resistant to host suppressor mechanisms. Evidence that they do so by activating contrasuppressor cells is discussed