title: Regulatory T-cell therapy in the induction of transplant tolerance: the issue of subpopulations.
abstract: Clinical tolerance induction to permit minimization or cessation of immunosuppressive drugs is one of the key research goals in solid organ transplantation. The use of ex vivo expanded or manipulated immunologic cells, including CD4CD25FOXP3 regulatory T cells (Tregs), to achieve this aim is already a reality, with several trials currently recruiting patients. Tregs are a highly suppressive, nonredundant, population of regulatory cells that prevent the development of autoimmune diseases in mammals. Data from transplanted humans and animal models support the notion that Tregs can mediate both induction and adoptive transfer of transplantation tolerance. However, human Tregs are highly heterogeneous and include subpopulations with the potential to produce the proinflammatory cytokine interleukin-17, which has been linked to transplant rejection. Tregs are also small in number in the peripheral circulation, thus they require ex vivo expansion before infusion into man. Selection of the most appropriate Treg population for cell therapy is, therefore, a critical step in ensuring successful clinical outcomes. In this review, we discuss Treg subpopulations, their subdivision based on nonmutually exclusive criteria of origin, expression of immunologic markers and function, availability in the peripheral blood of patients awaiting transplantation, and their suitability for programs of cell-based therapy.
authors.affiliation: 1 Medical Research Council Centre for Transplantation, King's College London, London, United Kingdom. 2 National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, London, United Kingdom. 3 Department of Immunobiology, King's College London, London, United Kingdom. 4 Address correspondence to: Behdad Afzali M.D., Ph.D., MRC Centre for Transplantation, Immunoregulation Laboratory, 5th Floor, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Francis C
authors.initials: FC
authors.lastname: Edozie
authors.forename: Estefania A
authors.initials: EA
authors.lastname: Nova-Lamperti
authors.forename: Giovanni A M
authors.initials: GA
authors.lastname: Povoleri
authors.forename: Cristiano
authors.initials: C
authors.lastname: Scottà
authors.forename: Susan
authors.initials: S
authors.lastname: John
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lombardi
authors.forename: Behdad
authors.initials: B
authors.lastname: Afzali
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000096:biosynthesis; D016030:Kidney Transplantation; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D023001:Transplantation Tolerance
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17