T regulatory cell therapy in transplantation:  stability, localization and functional specialization.
OBJECTIVE
There is great hope that cellular therapy with regulatory T cells (Tregs) will be an effective way to induce alloantigen specific tolerance, ultimately allowing for reduction or elimination of nonspecific immunosuppression. In the past, considerable effort was focused on defining the optimal ways to isolate and expand Tregs from peripheral or cord blood. Now that expansion of therapeutically relevant numbers of Tregs is feasible, we need to consider what is going to happen to the cells when they are transferred in vivo.


RESULTS
For optimal function, Tregs must be able to traffic to the correct location(s) and, despite the presence of immunosuppressive therapy, live long enough to transfer their regulatory function to recipient T cells. Within the Treg pool, there are also functionally specialized subsets, identified by chemokine receptor expression and/or cytokine production, which control their trafficking and relative ability to suppress different types of T helper cells, respectively. Recent findings imply that the plasticity of appropriately obtained populations of Tregs may not be of as great concern as previously suggested. Experimental data have also provided evidence as to how one might design adjunctive treatment that best supports the viability and function of Tregs after transfer.


CONCLUSIONS
Knowledge of how Tregs work in transplantation comes from studies that do not recapitulate how these cells will be used in humans. There is a need to develop better preclinical models to study how the in-vivo function of human Tregs can be optimized to ensure they can meet the challenge of inducing transplantation tolerance.
Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
Katherine G
KG
MacDonald
Paul C
PC
Orban
Megan K
MK
Levings
D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D007111:Immunity, Cellular; D007519:Isoantigens / Q000276:immunology; D016377:Organ Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D023001:Transplantation Tolerance / Q000276:immunology*
D007519:Isoantigens