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

Abstract

T regulatory cells (Tregs) play a vital role in suppressing heightened immune response, and thereby promote a state of immunological tolerance. Tregs modulate both innate and adaptive immunity, which makes them potential candidates for cell-based immunotherapy in the suppression of uncontrolled activation of graft-specific inflammatory cells and toxic mediators. Graft-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 shows promising results; however, key issues regarding Treg immunotherapy remain unresolved, including the mechanism of action and specific Treg cell phenotypes responsible for a state of tolerance. This review highlights the involvement of various subsets of Tregs during immune suppression, the novelty of Treg functions, effects on angiogenesis, emerging technologies for effective Treg expansion, and 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.