ovalbumin and Communicable-Diseases

Langerhans cells (LCs) are antigen-presenting dendritic cells (DCs) that reside in epithelia. The best studied example is the LC of the epidermis. By electron microscopy, their identifying feature is the unique rod- or tennis racket-shaped Birbeck granule. The phenotypic hallmark is their expression of the C-type lectin receptor langerin/CD207. Langerin, however, is also expressed on a recently discovered population of DC in the dermis and other tissues of the body. These 'dermal langerin(+) dendritic cells' are unrelated to LCs. The complex field of langerin-negative dermal DCs is not dealt with here. In this article, we briefly review the history, ontogeny, and homeostasis of LCs. More emphasis is laid on the discussion of functional properties in vivo. Novel models using genetically engineered mice are contributing tremendously to our understanding of the role of LCs in eliciting adaptive immune responses against pathogens or tumors and in inducing and maintaining tolerance against self antigens and innocuous substances in vivo. Also, innate effector functions are increasingly being recognized. Current activities in this area are reviewed, and possibilities for future exploitation of LC in medicine, e.g. for the improvement of vaccines, are contemplated.

Topics: Adaptive Immunity; Animals; Antigen Presentation; Antigens, CD; Antigens, Surface; Cell Lineage; Communicable Diseases; Dermatitis, Contact; Disease Models, Animal; Homeostasis; Humans; Immune Tolerance; Immunity, Innate; Langerhans Cells; Lectins, C-Type; Mannose-Binding Lectins; Mice; Mice, Transgenic; Neoplasms; Ovalbumin; Phenotype; Skin; Vaccines

Harnessing the ability of cytotoxic T lymphocytes (CTLs) to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs) following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4-6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS.

Topics: Animals; Antigens; CD8-Positive T-Lymphocytes; Cells, Cultured; Chickens; Communicable Diseases; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Immunologic Memory; Immunotherapy, Adoptive; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasms; Ovalbumin; T-Lymphocytes, Cytotoxic; Time Factors

Topics: Adolescent; Adult; Albumins; Animals; Antibodies; Antigen-Antibody Reactions; Cardiovascular Diseases; Cattle; Child; Collagen Diseases; Communicable Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; gamma-Globulins; Gastrointestinal Diseases; Hematologic Diseases; Humans; Hypersensitivity; Infant; Infant, Newborn; Insulin; Iodine Isotopes; Lactalbumin; Maternal-Fetal Exchange; Milk; Nervous System Diseases; Ovalbumin; Pregnancy; Respiratory Tract Diseases; Serum Albumin; Serum Albumin, Bovine; Skin Tests; Viral Vaccines