Donor Alloantigen Reactive Tregs (darTregs) for Calcineurin Inhibitor (CNI) Reduction

Study Enrollment Inclusion Criteria: * Subjects who meet all of the following criteria are eligible for enrollment: 1. Able to understand and provide informed consent 2. Have received a primary, solitary, living donor liver transplant more 24 months and less than 84 months ago 3. Have a living donor who is willing to consent to a one time blood draw of 100 mLs to enable the manufacture of Donor Alloantigen Reactive Regulatory T cells (darTregs) 4. Eighteen to 70 years of age at the time of study entry/consent 5. Liver function test (LFT) results: have Alanine Aminotransferase (ALT)consistently \<60 U/L and either alkaline phosphatase consistently \<150 U/L or Gamma-glutamyl transferase (GGT) consistently \<60 U/L 6. Currently receiving a Calcineurin Inhibitor (CNI) with 12 hour trough levels consistently \<6.0 ng/mL for tacrolimus; \<150 ng/mL for cyclosporine 7. Currently receiving CNI monotherapy or CNI and one of the following: 1. Prednisone: maximum dose of 5mg daily 2. Mycophenolate mofetil (MMF): maximum dose of 500 mg administered twice daily for Cellcept or 360mg twice daily for Myfortic. 8. Female and male participants with reproductive potential must agree to use effective methods of birth control for the duration of the study. 9. If history of Hepatocellular carcinoma (HCC), liver transplantation (LT) recipients who have: 1. α-fetoprotein (AFP) less than 100 μg/L at the time of transplant AND 2. Explanted liver: * with tumor burden within the Milan criteria and * without macro- or micro-vascular invasion and * without any lesions with poorly differentiated HCC and * without cholangiocarcinoma morphology 3. Risk Estimation of Tumor Recurrence After Transplant (RETREAT) Score less than or equal to 3 10. If history of HCC, at the time of enrollment, subjects must also: 1. Be 36 months or more post-transplant AND 2. Without evidence of recurrent HCC defined as: * AFP within normal limits for performing laboratory; * Confirmatory chest CT and * Confirmatory CT or MRI of the abdomen and pelvis. 11. If history of hepatitis C virus (HCV) , recipients must be: 1. Cured of HCV as defined by achieving Sustained virologic response (SVR) and be greater than or equal to six months after the end of treatment 2. HCV RNA negative at time of study enrollment Study Enrollment Exclusion Criteria: * Participants who meet any of these criteria are not eligible for study enrollment: 1. Transplant for liver disease secondary to autoimmune disease (e.g. autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cirrhosis) 2. Matched at both human leukocyte antigen (HLA)-DR loci to the donor 3. Organ, tissue or cell transplant prior to or after the primary solitary living donor liver transplant 4. For subjects with hepatitis B, detectible hepatitis B virus (HBV) DNA 5. History of malignancy within 5 years of enrollment. History of adequately treated in-situ cervical carcinoma and/or skin cancer (basal or squamous cell) will be permitted. 6. Serologic evidence of human immunodeficiency 1 or 2 infection 7. Epstein Barr Virus (EBV) seronegativity (EBV naïve) if living donor is EBV seropositive 8. Cytomegalovirus (CMV) seronegativity (CMV naïve) if living donor is CMV seropositive 9. Calculated Glomerular filtration rate (GFR) less than 50 mL/min/1.73m\^2 at the time of enrollment 10. An episode of Acute Rejection (AR) within one year of enrollment 11. Systemic illness requiring or likely to require recurrent or chronic immunosuppression (IS) drug use 12. Any chronic condition for which anti-coagulation cannot be safely interrupted for liver biopsy 13. Positive pregnancy test 14. Participation in any other studies that involved investigational drugs or regimens in the preceding year 15. Any other condition, in the investigator's judgment, that increases the risk of darTregs infusion or prevents safe trial participation 16. Unwilling or unable to adhere to study requirements and procedures 17. Screening liver biopsy with any of the following histological criteria, as determined by the reading of a central pathologist. darTregs Infusion Inclusion Criteria: * Subjects must meet all criteria below to receive darTregs infusion: 1. Stable liver tests, defined as ALT and either alkaline phosphatase or GGT either within normal limits OR \<\\=1.5 X baseline 2. No detectible circulating EBV or CMV DNA prior to Treg infusion, assessed at the time of PBMC collection for manufacture 3. For subjects with hepatitis B virus (HBV), no detectible circulating HBV DNA, assessed at the time of PBMC collection for manufacture 4. Able to understand and provide informed consent. darTregs Infusion Exclusion Criteria: Subjects who meet any of these criteria are not eligible for darTregs infusion: 1. Diagnosis of AR after initiation of IS withdrawal 2. Any vaccination given within 28 days prior to Treg collection for Treg production 3. Receipt of a vaccination within 14 days prior to Treg infusion 4. Unacceptable darTregs product 5. Positive pregnancy test 6. Clinical evidence of viral syndrome less than 7 days prior to darTregs infusion. Inclusion Criteria for Resuming IS Withdrawal after darTregs Infusion: Subjects are eligible to resume IS withdrawal after darTregs infusion if all criteria below are met: 1. Subject received at least 100 x 10\^6 darTregs 2. ALT and either alkaline phosphatase or GGT remain within normal limits or \<\\= 1.5 x baseline after darTregs infusion 3. For subjects with elevated liver tests as defined above, local pathology reading of liver biopsy 6-10 days after darTregs infusion is without AR according to Banff criteria 4. IS withdrawal resumes no later than 14 days after darTregs infusion 5. Site principal investigator determines it is acceptable for the study subject to resume IS withdrawal.