Regulatory T cells as therapeutic cells.
OBJECTIVE
Although a plethora of data indicate the importance of regulatory T cells (Tregs) in experimental and clinical transplantation, are we any closer to seeing these cells as therapeutic tools in the clinic? This review discusses the functional and practical aspects of using CD4+CD25hiFoxp3+ Tregs as cellular therapeutic products in clinical transplantation, focusing on the requirements in terms of phenotype, antigen specificity and preparation of Tregs.


RESULTS
Following the emergence of new phenotypic markers of Tregs as well as improved isolation methods, a few milestone clinical trials employing the adoptive transfer of Tregs are now underway. Although mounting data suggest that alloantigen-specific Tregs may provide higher therapeutic benefits in solid organ transplantation compared with polyclonal Tregs, it seems that the specificty of Treg selected for use will need to be tailored to each clinical transplantation setting. In addition, recent findings imply that immunosuppressive regimes will also need to be reevaluated in order to complement this therapeutic strategy.


CONCLUSIONS
Although many key questions about Tregs remain, we are undoubtedly entering an exciting era of Treg research in clinical transplantation. As renewed efforts focus on translational medical research, it seems as though, whether ready or not, Tregs are finally crossing from bench to bedside.
Sagoo
Pervinder
P
Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London, UK.
Lombardi
Giovanna
G
Lechler
Robert I
RI
D019264:Adoptive Transfer / Q000009:adverse effects; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002469:Cell Separation; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D016377:Organ Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D016896:Treatment Outcome
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens