Role of Th17 cells and interleukin 17 in graft-versushost disease and graft-versusleukemia reactivity - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 268

ch 13

Role of Th17 cells and
interleukin 17 in graft-versus-
host disease and graft-versus-
leukemia reactivity

Xiao Chen
Blood and Marrow Stem Cell Transplant Program and Department of Medicine, Medical College of Wisconsin,
Milwaukee, Wisconsin, USA
William R Drobyski
Blood and Marrow Stem Cell Transplant Program, Department of Pediatrics, Department of Microbiology, and
Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

271

Discovery of Th17 cells

CD4 + helper T cells play an important role in the initiation and regulation
of immune responses in vivo. Naïve CD4 + T cells proliferate and differenti-
ate into different effector subsets when they are activated and this is largely
influenced by the local cytokine milieu at the time of activation. Historically,
T-helper cells have been divided into two distinct subsets, termed T-helper
1 (Th1) and T-helper 2 (Th2), based on their distinct cytokine profiles and
effector functions [1] . Th1 cells secrete large amounts of interferon-γ (IFN-γ)
upon activation. These cells are important in mediating immune responses
and are highly effective at eradicating intracellular pathogens. On the other
hand, Th2 cells secrete interleukin 4 (IL-4), IL-5, and IL-13 and are mainly
involved in humoral immunity such as allergic immune responses and anti-
parasitic immunity [2] . In the last part of the 20th century, this Th1 and Th2
classification formed the basis of our understanding of CD4 + T-cell biology.
This paradigm, however, began to be altered in the mid-1990s when Rouvier
et al. [3] and then Yao and colleagues [4] described a new cytokine in mice,
which they termed IL-17 and which had homology to a gene in herpesvirus
saimiri. The human counterpart of murine IL-17 was soon cloned by Fossiez
and colleagues [5] . A number of studies quickly established that IL-17 had
proinflammatory properties and could induce the production of inflam-
matory cytokines such as IL-1β, tumor necrosis factor-α (TNF-α), IL-6, and
IL-8 along with hematopoietic cytokines such as granulocyte colony-stim-
ulating factor (G-CSF) [5,6] . The elucidation of Th17 cells as another CD4 +
T-cell subset, however, did not come for several more years and was facili-
tated by the discovery of IL-23, which was identified as a member of the