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2015 ; 6
(ä): 438
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Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance
in Transplantation
#MMPMID26379673
Safinia N
; Scotta C
; Vaikunthanathan T
; Lechler RI
; Lombardi G
Front Immunol
2015[]; 6
(ä): 438
PMID26379673
show ga
Regulatory T cells (Tregs) play an important role in immunoregulation and have
been shown in animal models to promote transplantation tolerance and curb
autoimmunity following their adoptive transfer. The safety and potential
therapeutic efficacy of these cells has already been reported in Phase I trials
of bone-marrow transplantation and type I diabetes, the success of which has
motivated the broadened application of these cells in solid-organ
transplantation. Despite major advances in the clinical translation of these
cells, there are still key questions to be addressed to ensure that Tregs attest
their reputation as ideal candidates for tolerance induction. In this review, we
will discuss the unique traits of Tregs that have attracted such fame in the
arena of tolerance induction. We will outline the protocols used for their ex
vivo expansion and discuss the future directions of Treg cell therapy. In this
regard, we will review the concept of Treg heterogeneity, the desire to isolate
and expand a functionally superior Treg population and report on the effect of
differing culture conditions. The relevance of Treg migratory capacity will also
be discussed together with methods of in vivo visualization of the infused cells.
Moreover, we will highlight key advances in the identification and expansion of
antigen-specific Tregs and discuss their significance for cell therapy
application. We will also summarize the clinical parameters that are of
importance, alongside cell manufacture, from the choice of immunosuppression
regimens to the number of injections in order to direct the success of future
efficacy trials of Treg cell therapy. Years of research in the field of tolerance
have seen an accumulation of knowledge and expertise in the field of Treg
biology. This perpetual progression has been the driving force behind the many
successes to date and has put us now within touching distance of our ultimate
success, immunological tolerance.