ovalbumin and Infections

Topics: Animals; Animals, Newborn; Bacterial Infections; Blood Bactericidal Activity; Body Temperature; Chick Embryo; Chickens; Egg Proteins; Egg Shell; Female; Infections; Intestines; Muramidase; Mycoses; Ovalbumin; Phagocytosis; Skin; Transferrin; Virus Diseases; Vitelline Membrane

T lymphocytes responding to microbial infection give rise to effector cells that mediate acute host defense and memory cells that provide long-lived immunity, but the fundamental question of when and how these cells arise remains unresolved. Here we combined single-cell gene-expression analyses with 'machine-learning' approaches to trace the transcriptional 'roadmap' of individual CD8(+) T lymphocytes throughout the course of an immune response in vivo. Gene-expression signatures predictive of eventual fates could be discerned as early as the first T lymphocyte division and may have been influenced by asymmetric partitioning of the receptor for interleukin 2 (IL-2Rα) during mitosis. Our findings emphasize the importance of single-cell analyses in understanding fate determination and provide new insights into the specification of divergent lymphocyte fates early during an immune response to microbial infection.

Topics: Adaptive Immunity; Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Lineage; Computer Simulation; Gene Expression Profiling; Infections; Listeria monocytogenes; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitosis; Ovalbumin; Receptors, Interleukin-2; Single-Cell Analysis; T-Lymphocyte Subsets; Transcriptional Activation

Professional APCs of hemopoietic-origin prime pathogen-specific naive CD8 T cells. The primed CD8 T cells can encounter Ag on infected nonhemopoietic cell types. Whether these nonhemopoietic interactions perpetuate effector T cell expansion remains unknown. We addressed this question in vivo, using four viral and bacterial pathogens, by comparing expansion of effector CD8 T cells in bone marrow chimeric mice expressing restricting MHC on all cell types vs mice that specifically lack restricting MHC on nonhemopoietic cell types or radiation-sensitive hemopoietic cell types. Absence of Ag presentation by nonhemopoietic cell types allowed priming of naive CD8 T cells in all four infection models tested, but diminished their sustained expansion by approximately 10-fold during lymphocytic choriomeningitis virus and by < or =2-fold during vaccinia virus, vesicular stomatitis virus, or Listeria monocytogenes infections. Absence of Ag presentation by a majority (>99%) of hemopoietic cells surprisingly also allowed initial priming of naive CD8 T cells in all the four infection models, albeit with delayed kinetics, but the sustained expansion of these primed CD8 T cells was markedly evident only during lymphocytic choriomeningitis virus, but not during vaccinia virus, vesicular stomatitis virus, or L. monocytogenes. Thus, infected nonhemopoietic cells can amplify effector CD8 T cell expansion during infection, but the extent to which they can amplify is determined by the pathogen. Further understanding of mechanisms by which pathogens differentially affect the ability of nonhemopoietic cell types to contribute to T cell expansion, how these processes alter during acute vs chronic phase of infections, and how these processes influence the quality and quantity of memory cells will have implications for rational vaccine design.

Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Bone Marrow Cells; CD8-Positive T-Lymphocytes; Chimera; Clone Cells; Infections; Listeria monocytogenes; Lymphocyte Activation; Lymphocytic choriomeningitis virus; Mice; Mice, Mutant Strains; Mice, Transgenic; Ovalbumin; Receptors, Antigen, T-Cell; Vaccinia virus; Vesicular stomatitis Indiana virus

Costimulatory signals from dendritic cells (DCs) are required for naive T cells to respond to antigenic stimulation. To what extent DCs reactivate memory T cells during recall responses is not known. Here, an in vivo depletion system has been used to analyze the role of DCs in reactivating CD8 memory T cells during recall responses to three different microbial infections. We show a profound decrease in the numbers of responding memory CD8 T cells in both lymphoid and nonlymphoid tissues during the recall responses to infection with vesicular stomatitis virus, Listeria monocytogenes (Lm), or influenza virus. These data show that interaction with DCs is a major mechanism driving T cell reactivation in vivo, even during a tissue-specific infection of the respiratory tract.

Topics: Animals; CD8-Positive T-Lymphocytes; Chimera; Dendritic Cells; Green Fluorescent Proteins; Heparin-binding EGF-like Growth Factor; Immunologic Memory; Infections; Intercellular Signaling Peptides and Proteins; Listeriosis; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Orthomyxoviridae Infections; Ovalbumin; Receptors, Cell Surface; Rhabdoviridae Infections; Signal Transduction; Vesicular stomatitis Indiana virus