ovalbumin and Lymphatic-Diseases

Apoptotic death of T lymphocytes is critical for shutdown of immune responses and hemopoietic cell homeostasis. Both death receptor (Fas) activation and mitochondrial apoptosis triggered by the BH3-only protein Bim have been implicated in the killing of antigen-stimulated T cells. We examined mice lacking the gene encoding Bim (Bcl2l11) and with the inactivating lpr mutation in the gene encoding Fas (Fas), designated Bcl2l11(-/-)Fas(lpr/lpr) mice. Shutdown of an acute T cell response to herpes simplex virus involved only Bim with no contribution by Fas, whereas both pathways synergized in killing antigen-stimulated T cells in chronic infection with murine gamma-herpesvirus. Bcl2l11(-/-)Fas(lpr/lpr) mice developed remarkably enhanced and accelerated fatal lymphadenopathy and autoimmunity compared to mice lacking only one of these apoptosis inducers. These results identify critical overlapping roles for Fas and Bim in T cell death in immune response shutdown and prevention of immunopathology and thereby resolve a long-standing controversy.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Autoimmunity; Bcl-2-Like Protein 11; CD8-Positive T-Lymphocytes; Chronic Disease; fas Receptor; Gammaherpesvirinae; Herpes Simplex; Herpesviridae Infections; Herpesvirus 1, Human; Lymphatic Diseases; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Ovalbumin; Proto-Oncogene Proteins; T-Lymphocyte Subsets

Alymphoplasia (aly/aly) mice are from a naturally occurring strain with a mutation in nuclear factor-kappa B inducing kinase (NIK). The NIK mutation causes disruption of the architecture of the thymus and spleen and aly/aly mice show decreased numbers of CD25+CD4+T cells in the spleen. For the expansion of CD25+CD4+T cells, interactions between dendritic cells (DCs) and CD25+CD4+ regulatory T cells are necessary. We investigated the ability of DCs to induce expansion of CD25+CD4+T cells. We found that DCs are reduced in the spleen of aly/aly mice, and showed low expressions of CD80, CD86 and MHC class II molecules on the surface. DCs from aly/aly mice showed decreased ability to present ovalbumin (OVA) to T cells from OVA specific TCR transgenic mice, and a decreased ability for alloantigen presentation. Further, DCs showed a decreased ability to induce expansion of CD25+CD4+T cells in vitro. Our results suggested that the impairment of DCs in aly/aly mice is responsible, at least in part, for the decreased numbers of CD25+CD4+T cells in the periphery of aly/aly mice.

Topics: Animals; Antigen Presentation; B7-1 Antigen; B7-2 Antigen; CD4 Antigens; Cell Differentiation; Cells, Cultured; Dendritic Cells; Genes, MHC Class II; Interleukin-2 Receptor alpha Subunit; Lymphatic Diseases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin; Spleen; T-Lymphocytes, Regulatory

Infections can influence concurrent and subsequent Th1 vs Th2 immune responses to Ags. Through pattern recognition of foreign unmethylated CpG dinucleotides, the vertebrate innate immune system can sense infectious danger and typically replies with a Th1-polarized adaptive immune response. We examined whether CpG-DNA exposure would influence subsequent responses to infection and soluble Ags. CpG-DNA injection led to local lymphadenopathy characterized by maintenance of cellular composition with some biasing toward elevated dendritic cell composition. Sustained local production of IL-12 and IFN-gamma from dendritic cells and T cells was shown. Prior injection by up to 2 wk with CpG-DNA protected BALB/c mice from Th2 driven lethal leishmaniasis. CpG-DNA injection by up to 5 wk before soluble Ag challenge resulted in the generation of Ag-specific CTL, Th1 recall responses to Ag, and Th1-polarized Ag-specific Abs. Thus, CpG-DNA instigated a local predisposition for intense CTL responses and Th1-polarized immune responses to subsequent infections or Ag challenge. The induction by the innate immune system of a locally contained hypersensitivity could represent a capacitating immune reaction yielding rapid conditioned responses to secondary infections.

Topics: Adoptive Transfer; Animals; Antigens; CD11 Antigens; CpG Islands; Cytotoxicity, Immunologic; DNA; Female; Immunity, Cellular; Immunity, Innate; Immunization; Injections, Subcutaneous; Interferon-gamma; Interleukin-12; Kinetics; Leishmania major; Leishmaniasis, Cutaneous; Lymph Nodes; Lymphatic Diseases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Oligonucleotides; Ovalbumin; T-Lymphocytes, Cytotoxic; Th1 Cells

Immunoreactivity for S-100 protein was investigated immunohistochemically in a series of 49 fixed and paraffin-embedded normal, reactive, and neoplastic human lymphoid tissue specimens. The avidin-biotin complex immunoperoxidase method was used, with overnight (12-hour) incubation with a commercially available antiserum to S-100 protein. In addition, cryostat sections were tested with DRC 1 monoclonal antibody to dendritic reticulum cells (DRCs) in three cases and with OKT6 antibody to interdigitating reticulum cells (IRCs) in nine cases. All tissues, including lymph nodes, tonsils, adenoid, spleens, appendices, thymuses, and tissues containing nodular reactive lymphoid infiltrates, demonstrated a consistent immune staining pattern. A striking network composed of dendritic processes that showed finely granular S-100 protein immunoreactivity was observed in most of the follicular germinal centers; a similar dendritic pattern was observed in the follicular centers when the corresponding frozen sections were immunostained with DRC 1. In the extrafollicular areas, the S-100-positive cells topographically and morphologically resembled the IRCs that were demonstrated by OKT6 antibody in the corresponding frozen sections. The results seem to indicate that cells topographically and morphologically similar to IRCs and DRCs in human lymphoid tissues from different sites share immunoreactivity for S-100 protein. The present study confirms the unexpected presence of S-100 protein in dendritic cells of follicular germinal centers by a simple and currently available method.

Topics: Antibodies, Monoclonal; Avidin; Biotin; Humans; Hyperplasia; Immune Sera; Immunologic Techniques; Lymph Nodes; Lymphatic Diseases; Lymphoid Tissue; Lymphoma; Ovalbumin; S100 Proteins; Staining and Labeling; Tissue Distribution

Topics: Avidin; Biotin; Histocytochemistry; Humans; Immunochemistry; Lymph Nodes; Lymphatic Diseases; Ovalbumin; Palatine Tonsil