Th1/Th2 and Tc1/Tc2 cells: biology, experimental models and clinical translation - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 237

clinical allogeneic hematopoietic cell transplantation. In an attempt to
bridge this translational divide, several lines of clinical research might be
pursued. First, it would be helpful to develop common criteria to quan-
tify allograft T-helper cell subset content using state-of-the-art methods,
including assessment of differentiation status, chemokine receptor expres-
sion, cytokine secretion potential, and transcription factor expression.
Only through careful and extensive efforts in this vein will one be able to
address whether allograft Th1/Th2 content helps determine clinical trans-
plantation outcome; unfortunately, the field is not close to accomplishing
this task of characterizing allograft content at a functional level, as even
CD4 + and CD8 + T-cell content information is not collected routinely by
the Center for International Blood and Marrow Transplantation Research.

It is more likely that advances in our clinical understanding of the Th1/Th2
paradigm in transplantation will therefore emanate from single institutions
or small group interactions between individuals adept in the measurement
of functional allograft T-cell content and its relationship to post-transplant
T-cell phenotype. And finally, allograft T-cell engineering to purposefully
control the allograft content of Th1 and Th2 cells may provide a more direct
pathway to address whether this biology can be harnessed for therapeu-
tic gain. As detailed in this chapter, attempts to control this Th1/Th2 bal-
ance must consider many factors pertaining to ex vivo T-cell manufacture
(methods of selection, stimulation, cytokine polarization and functional
modification through agents such as rapamycin); the combinations and
permutations of manufacturing methods are vast and will increase as new
immune and cellular pathways and reagents are identified or become avail-
able in good manufacturing practice grade. Preclinical analysis of manufac-
tured T-cell products may be facilitated through use of human-into-mouse
transplantation models. However, carefully designed and implemented
clinical trials will be required to ultimately determine whether the Th1/
Th2 immune modulation pathway can be manipulated for therapeutic gain
after allogeneic HCT.

240

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