1;Contents;6 2;Contributors;8 3;TIM-3 and Its Regulatory Role in Immune Responses;10 3.1;1 Introduction;11 3.2;2 Protein Structure;11 3.3;3 TIM-3 Ligands;13 3.3.1;3.1 Identification of Galectin-9 as a TIM-3 Ligand;13 3.3.2;3.2 Phosphatidylserine as a TIM-3 Ligand;14 3.3.3;3.3 Carbohydrate Ligands for TIM-3;15 3.4;4 Expression of TIM-3;15 3.4.1;4.1 Transcriptional Control of TIM-3 Expression;16 3.5;5 TIM-3 in Disease;16 3.5.1;5.1 Genetic Basis for Role of TIM-3 in Disease;16 3.6;6 TIM-3 in Autoimmune Diseases;17 3.6.1;6.1 TIM-3 in Chronic Viral Infection;18 3.6.2;6.2 TIM-3 in Other Diseases;20 3.7;7 Conclusions;20 3.8;References;21 4;Role of PD-1 in Regulating T-Cell Immunity;25 4.1;1 Identification of PD-1 and Its Ligands;26 4.2;2 Structure of PD-1 and Its Ligands;27 4.3;3 Regulation of PD-1 Expression;29 4.4;4 PD-1 Signaling: Molecular Mechanisms of Inhibition;30 4.5;5 Biological Significance of PD-1;32 4.5.1;5.1 PD-1 in Autoimmunity;32 4.5.2;5.2 PD-1 in Chronic Viral Infection;34 4.5.3;5.3 PD-1 in Antitumor Immunity;35 4.6;6 Conclusions;37 4.7;References;38 5;The Role of IL-10 in Regulating Immunity to Persistent Viral Infections;46 5.1;1 Introduction;47 5.1.1;1.1 Immune Dynamics During Acute and Persistent Virus Infection: The Failure of Antiviral Immunity;47 5.2;2 The Impact of Host-Based Regulatory Mechanisms in T Cell Exhaustion;49 5.2.1;2.1 Discovery That Host-Based Suppressive Factors Inhibit Clearance of Persistent Viral Infection;49 5.2.2;2.2 Multiple Regulatory Factors Suppress T Cell Responses During Viral Persistence;50 5.2.3;2.3 Differential Impact of Reversing T Cell Exhaustion During Viral Persistence;51 5.3;3 The Impact of IL-10 Toward Viral Persistence;52 5.3.1;3.1 The Diverse Roles of IL-10 During Viral Infection;52 5.3.2;3.2 Sources, Mechanisms, and Targets of IL-10 During Persistent Viral Infection;54 5.4;4 Targeting Immunosuppression: Potential Therapeutic Applications for Blocking IL-10;60 5.5;5 Past, Present, and Future;64 5.6;References;65 6;Inhibitory Ly49 Receptors on Mouse Natural Killer Cells;73 6.1;1 Introduction;74 6.2;2 Ly49 Haplotypes and Ligands;74 6.3;3 Inhibitory Signaling Events;80 6.4;4 Educational Impact of Ly49 Receptors on NK Cells;82 6.5;5 Inhibitory Ly49 Receptors and Viral Infections;84 6.6;6 Inhibitory Ly49 Receptors in Transplantation and Malignancy;85 6.7;7 Concluding Remarks;87 6.8;References;87 7;Immunoregulatory Roles for Fc Receptor-Like Molecules;94 7.1;1 Introduction;95 7.2;2 Identification of FCRL Molecules Reveals a New Level of B Cell Regulation;95 7.3;3 FCRL Structural Properties;96 7.4;4 FCRL Expression Patterns;99 7.5;5 FCRL Functional Properties;101 7.6;6 FCRL Involvement in Human Diseases;103 7.7;7 Concluding Remarks;105 7.8;References;106 8;FcgammaRs in Health and Disease;110 8.1;1 Introduction;111 8.2;2 The Family of Canonical Fcgamma-Receptors;112 8.3;3 Regulation of IgG Activity In Vivo;114 8.4;4 Influence of Antibody Glycosylation and Novel Fcgamma-Receptors;116 8.5;5 Role of FcgammaRs for Infection;118 8.6;6 Microbial Immune Escape Mechanisms Targeting the IgG-FcgammaR Interaction;121 8.7;7 Other Ligands for Fcgamma-Receptors;122 8.8;8 Conclusions;123 8.9;References;124 9;TGF-beta Function in Immune Suppression;131 9.1;1 Introduction;132 9.2;2 TGF-beta and Signal Transduction;132 9.3;3 How TGF-beta Inhibits Immune Responses;133 9.4;4 Induction and Regulation of Treg-Differentiation by TGF-beta;135 9.5;5 Molecular Mechanism of Foxp3 Induction by TGF-beta;137 9.6;6 TGF-beta and Th17 Differentiation;138 9.7;7 Regulation of Effector Th-Differentiation by TGF-beta;139 9.8;8 Treg Is a Major Source of Pro-TGF-beta, and TGF-beta Is One of the Effector Molecules of Tregs;139 9.9;9 Smad-Dependent and Smad-Independent Regulation of Th Differentiation by TGF-beta;140 9.10;10 Smad-Mediated Suppression of the Cytokine Production;142 9.11;11 Reciprocal Regulation of TGF-beta Signaling and IFN-gamma Signaling;143 9.12;12 Conclusions;144 9.13;References;145 10;Index;152