Autophagy is a specialized cellular pathway involved in maintaining homeostasis by degrading long-lived cellular proteins and organelles. Recent studies have demonstrated that autophagy is utilized by immune systems to protect host cells from invading pathogens and regulate uncontrolled immune responses. During pathogen recognition, induction of autophagy by pattern recognition receptors leads to the promotion or inhibition of consequent signaling pathways. Furthermore, autophagy plays a role in the delivery of pathogen signatures in order to promote the recognition thereof by pattern recognition receptors. In addition to innate recognition, autophagy has been shown to facilitate MHC class II presentation of intracellular antigens to activate CD4 T cells. In this review, we describe the roles of autophagy in innate recognition of pathogens and adaptive immunity, such as antigen presentation, as well as the clinical relevance of autophagy in the treatment of human diseases.
Adaptive Immunity/immunology/*physiology ; Animals ; Antigen Presentation/immunology/physiology ; Autophagy/immunology/*physiology ; Humans ; Major Histocompatibility Complex/immunology/physiology

The profound graft-versus-leukemia (GVL) effect presented after allogeneic hematopoietic cell transplantation (allo-HSCT) has been evidenced. In contrast to T cell mediated GVL, natural killer (NK) cells recognize target cells and introduce GVL effect by using an integration of activating and inhibitory receptors. This review has summarized current literatures from 2001 - 2003 on human killer cell immunoglobulin receptors (KIR) and other NK cell receptors involved in recognition of tumor targets and the polymorphism of KIR genes of donor/recipient pairs of related and unrelated Allo-HSCT. KIR epitope mismatch may facilitate engraftment and reduce leukemia relapse post transplant by mediating lysis of recipient's cells and introducing GVL effect under the condition of KIR epitope mismatch. Clinical roles of KIR in Allo-HSCT and immunotherapy are discussed. Technologic approach in allogeneic reactive NK cells introduction, identification and selection in vitro, development of inhibitory receptor blockade as well as up-regulation of activating NK cells may significantly enhance GVL immune response. Further investigation on the regulation of KIR inhibitory receptors enables to design novel strategy in cancer immunotherapy over the forthcoming decade.
Graft vs Host Disease ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Tolerance ; Killer Cells, Natural ; immunology ; Major Histocompatibility Complex ; Receptors, Immunologic ; chemistry ; genetics ; physiology ; Receptors, KIR ; Transplantation, Homologous

T cell anergy has been successfully induced under different conditions in cloned CD4(+) T cells, but induction of T cell anergy in vivo has been difficult and controversial. Due to the low frequency of naturally occurring T cell population with specificity to a defined antigen, it is very difficult to study anergy of naïve T cells without prior in vivo priming which complicates the interpretation of experimental data. To solve this problem, we adopted the HNT-TCR transgenic mice which have homogeneous antigen specific CD4(+) T cell population. In this study, we generated an influenza virus hemagglutinin (HA) peptide-specific CD4(+) T cell clone from the HNT-TCR transgenic mice and induced anergy using APCs which were treated with the crosslinker, ECDI (1-ethyl-3-3(3-dimethylaminopropyl) carbodiimide). The proliferative response of the cloned or freshly purified naïve CD4(+) transgenic T cells after treatment with ECDI-treated APCs and the HA peptide antigen was monitored as the index of anergy induction. The results showed that anergy was successfully induced in the cloned HNT-TCR transgenic CD4(+) T cells. It was determined that the induced anergy was antigen- and MHC-specific. By contrast, anergy was not observed in freshly purified naïve CD4(+) transgenic T cells under the same conditions. The results suggest that naïve CD4(+) T cells may have different anergy inducing requirements, or that cloned CD4(+) T cells may have certain priming or in vitro cloning artifact which makes them more susceptible to anergy induction. We propose that induction of T cell anergy may depend on the T cell growth, activation and differentiation state or cloning conditions. The results from the present study may have important implications for the study of the mechanism(s) underlying T cell anergy induction in vivo and for applications of immune tolerance based therapy.
Animals ; Antigen-Presenting Cells ; immunology ; metabolism ; Antigens, CD ; genetics ; immunology ; metabolism ; CD4 Antigens ; immunology ; CD4-Positive T-Lymphocytes ; cytology ; immunology ; Clonal Anergy ; genetics ; immunology ; Clone Cells ; immunology ; Epitopes, T-Lymphocyte ; biosynthesis ; Immune Tolerance ; genetics ; Major Histocompatibility Complex ; immunology ; Mice ; Mice, Transgenic ; Receptors, Antigen, T-Cell ; physiology