University of Maryland, Baltimore

Study Entry: 1. Subject and/or parent guardian must be able to understand the purpose of the study and willing to participate and sign informed consent/assent 2. Greater than or equal to 30 kg body weight 3. Listed for a primary lung transplant 4. No previous or planned desensitization therapy prior to transplant 5. Serum Immunoglobulin G (IgG) level greater than 400 mg/dL. Patients treated with intravenous immune globulin (IVIG) for hypogammaglobulinemia are eligible for enrollment if their serum IgG level is greater than 400 mg/dL 14 or more days after the most recent IVIG treatment 6. For women of child-bearing potential, willingness to use highly-effective contraception; according to the Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol). Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study. Those who choose oral contraception must agree to use a second form of contraception after administration of study drug for a period of 1 year after the last dose of study drug 7. Tested negative for latent TB infection (LTBI) using a PPD or interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB) within 1 year prior to transplant or has completed appropriate LTBI therapy within the 1 year prior to transplant 8. In the absence of contraindication, vaccinations must be up to date per the Division of Allergy, Immunology, and Transplantation (DAIT) Guidance for Patients in Transplant Trials Randomization: 1. Provide written informed consent for the study participation, and agree to continue in the study 2. Undergoing single or bilateral lung transplant 3. Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for the duration of the study. Those who choose oral contraception must agree to use a second form of contraception after administration of study drug for a period of 1 year after the last dose of study drug 4. Negative physical crossmatch, if the results are available at the time of randomization 5. No desensitization therapy prior to transplant 6. Negative pregnancy test (serum or urine) for women of child-bearing potential within 48 hours prior to transplant 7. Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Polymerase Chain Reaction (PCR) testing for the recipient prior to transplant as per institutional policy 8. Negative SARS-CoV2 PCR testing for the donor prior to transplant as per institutional policy 9. Recipient of lungs that have been supported with ex vivo lung perfusion (EVLP) devices are permitted

Study Entry: 1. Listed for multi-organ transplant (e.g., heart-lung, liver-lung, kidney-lung) 2. Prior history of organ or cellular transplantation 3. Received treatment to deplete Human Leukocyte Antigens (HLA) antibodies before transplantation 4. Currently breast-feeding a child or plans to become pregnant during the timeframe of the study follow up period 5. History of severe allergic and/or anaphylactic reactions to humanized or murine monoclonal antibodies 6. Known hypersensitivity or previous treatment with ACTEMRA(R) (tocilizumab) 7. Infection with human immunodeficiency virus (HIV) 8. Hepatitis B virus surface antigen or core antibody positive 9. Hepatitis C virus PCR positive (HCV+) patients who have failed to demonstrate sustained viral remission (2 consecutive PCR or Nucleic Acid Tests (NAT) negative tests at least 24 weeks apart), with or without anti-viral treatment; 10. Chronic infection with Burkholderia cenocepacia or Burkholderia gladioli 11. Non-tuberculous mycobacterial (NTM) pulmonary disease; if there is a history of NTM pulmonary disease, culture conversion is necessary for eligibility 12. Presence of active malignancy or history of malignancy less than 5 years in remission, excluding adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, or adequately treated basal or squamous cell carcinoma of the skin 13. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura 14. History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy) 15. Current treatment with alkylating agents such as cyclophosphamide 16. History of gastrointestinal (GI) tract perforation 17. History of inflammatory bowel disease except fully excised ulcerative colitis 18. History of diverticulitis (diverticulosis is not an exclusion) or diverticular bleeding; 19. Patients with a platelet count < 100,000/mm^3 (last measurement within 7 days prior to enrollment) 20. Patients with an absolute neutrophil count (ANC) < 2,000/mm^3 (last measurement within 7 days prior to enrollment) 21. Patients with Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) levels >3 times upper limit of normal 22. Patients who use illegal drugs 23. Use of investigational drugs within 4 weeks prior to enrollment 24. Any condition that in the opinion of the site Principal Investigator (PI) introduces undue risk by participating in this study Randomization: 1. Recipient of multi-organ or tissue transplants 2. Received a live virus vaccine within 30 days prior to randomization 3. Received treatment to deplete HLA antibodies before transplantation to improve the possibility of transplantation 4. Patients with known donor-specific antibody that will require intervention based on local clinical protocols 5. History of GI tract perforation 6. History of inflammatory bowel disease except fully excised ulcerative colitis 7. History of diverticulitis (diverticulosis is not an exclusion) or diverticular bleeding 8. History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies 9. Known hypersensitivity or previous treatment with ACTEMRA(R) (tocilizumab) 10. Recipient or donor with infection with human immunodeficiency virus (HIV) 11. Recipient with hepatitis B virus surface antigen or hepatitis B core antibody positive 12. Hepatitis B negative transplant recipient that received a transplant from a Hepatitis B core antibody positive donor unless the recipient has a Hepatitis B Surface Antigen (HBsAb) titer >10U/L 13. Recipient of a hepatitis C virus nucleic acid test (NAT) positive donor organ 14. Latent TB infection (LTBI) and has not completed appropriate therapy 15. Chronic infection with Burkholderia cenocepacia or Burkholderia gladioli 16. Non-tuberculous mycobacterial (NTM) pulmonary disease; if there is a history of NTM pulmonary disease, culture conversion is necessary for eligibility 17. Presence of active malignancy (except for non-melanoma skin cancer) 18. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura 19. History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy) 20. Current treatment with alkylating agents such as cyclophosphamide 21. Patients with AST or ALT levels > 1.5 times upper limit of normal (last measurement within 1 day prior to randomization) 22. Patients with platelet count <100,000/mm^3 (last measurement within 1 day prior to randomization) 23. Patients with an absolute neutrophil count (ANC) <2,000/mm^3 (last measurement within 1 day prior to randomization) 24. Patients who are administered or intended to be administered cytolytic (such as anti-thymocyte globulin) or anti-CD25 monoclonal antibody agents as induction therapy in the immediate post- transplant period 25. Patients who have been treated in the past 3 months, or for whom it is anticipated that treatment with any immunomodulatory biological agents post-transplant are excluded 26. Use of an investigational drug after transplant 27. Any condition that in the opinion of the site PI introduces undue risk by participating in this study