title: Current landscape for T-cell targeting in autoimmunity and transplantation.
abstract: In recent years, substantial advances in T-cell immunosuppressive strategies and their translation to routine clinical practice have revolutionized management and outcomes in autoimmune disease and solid organ transplantation. More than 80 diseases have been considered to have an autoimmune etiology, such that autoimmune-associated morbidity and mortality rank as third highest in developed countries, after cardiovascular diseases and cancer. Solid organ transplantation has become the therapy of choice for many end-stage organ diseases. Short-term outcomes such as patient and allograft survival at 1 year, acute rejection rates, as well as time course of disease progression and symptom control have steadily improved. However, despite the use of newer immunosuppressive drug combinations, improvements in long-term allograft survival and complete resolution of autoimmunity remain elusive. In addition, the chronic use of nonspecifically targeted immunosuppressive drugs is associated with significant adverse effects and increased morbidity and mortality. In this article, we discuss the current clinical tools for immune suppression and attempts to induce long-term T-cell tolerance induction as well as much-needed future approaches to produce more short-acting, antigen-specific agents, which may optimize outcomes in the clinic.
authors.affiliation: Tolera Therapeutics Inc, 350 E Michigan Ave Ste 205, Kalamazoo, MI 49007, USA. d-getts@northwestern.edu
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Getts
authors.forename: Sushma
authors.initials: S
authors.lastname: Shankar
authors.forename: Emily M L
authors.initials: EM
authors.lastname: Chastain
authors.forename: Aaron
authors.initials: A
authors.lastname: Martin
authors.forename: Meghann Teague
authors.initials: MT
authors.lastname: Getts
authors.forename: Kathryn
authors.initials: K
authors.lastname: Wood
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D065095:Calcineurin Inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors; D016377:Organ Transplantation / Q000379:methods*; D010880:Piperidines; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014181:Transplantation Immunology / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology
chemical_list: D065095:Calcineurin Inhibitors; D016207:Cytokines; D007166:Immunosuppressive Agents; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D011799:Quinazolines; D018121:Receptors, Cytokine; C543528:sotrastaurin; C479163:tofacitinib; D053616:Janus Kinase 3; D011493:Protein Kinase C