Th1/Th2 and Tc1/Tc2 cells: biology, experimental models and clinical translation - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 220

ch 11

Th1/Th2 and Tc1/Tc2 cells:
biology, experimental models
and clinical translation

Daniel H Fowler
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

T-helper differentiation
Overview

223

In 1986, Mosmann and Coffman made the seminal discovery that murine
CD4 + T-cell clones could be characterized not only on the basis of their
antigen specificity but also by their functional skill sets, defined initially
by differential cytokine secretion profiles [1] . Fast forward to the current
state, in which one can consider whether this Th1/Th2 paradigm might
have relevance both in terms of determining the natural history of key
transplantation responses (graft-versus-tumor (GVT) effects, graft rejec-
tion, graft-versus-host disease (GVHD)) and in terms of designing safer
and more effective methods of allogeneic hematopoietic cell transplanta-
tion (HCT).

Figure 11.1 details several key features in the development of Th1 and Th2
cells in the expanding universe of CD4 + T-helper cell differentiation that
now includes not only regulatory T (Treg) cells and Th17 cells (see Chapters
12 and 13, respectively) but other subsets of lesser known biology and rel-
evance to transplantation (including the Th9 [2] and T follicular helper [3]
subsets). This chapter focuses on the “conventional” Th1 and Th2 subsets
(and to a lesser degree, their CD8 + T-cell counterparts, the Tc1 and Tc2 sub-
sets), with some discussion of the Treg and Th17 populations to highlight
the dynamic interactions and balance between subsets and to address the
emerging phenomenon of T-helper subset interconversion that has been
coined “plasticity.” [4]

First, the Th1 and Th2 subsets are classically derived from a naïve and cyto-
kine nonpolarized subset of CD4 + T cells that is plentiful in newborn mice
and human umbilical cord blood, but represents a minority population in
the adult human allogeneic transplant donor. Herein lies one of the first
caveats in this bench-to-bedside consideration of Th1/Th2 biology as it
relates to allogeneic HCT: extremes of T-cell cytokine polarity are relatively
easily achieved in experimental models that have greater representation
from naïve CD4 + T cells and are more difficult to attain in the clinical setting,