T regulatory cell mediated immunotherapy for solid organ transplantation: A clinical perspective.

T regulatory cells (Tregs) play a vital role in suppressing heightened immune responses, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which make them a potential candidate for cell-based immunotherapy to suppress uncontrolled activation of graft specific inflammatory cells and their toxic mediators. These grafts specific inflammatory cells (T effector cells) and other inflammatory mediators (Immunoglobulins, active complement mediators) are mainly responsible for graft vascular deterioration followed by acute/chronic rejection. Treg mediated immunotherapy is under investigation to induce allospecific tolerance in various ongoing clinical trials in organ transplant recipients. Treg immunotherapy is showing promising results but the key issues regarding Treg immunotherapy are not yet fully resolved including their mechanism of action, and specific Treg cell phenotype responsible for a state of tolerance. This review highlights the involvement of various subsets of Tregs during immune suppression, novelty of Tregs functions, effects on angiogenesis, emerging technologies for effective Treg expansion, plasticity and safety associated with clinical applications. Altogether this information will assist in designing single/combined Treg mediated therapies for successful clinical trials in solid organ transplantations.