Recent advances in graft‐versus‐host disease (GVHD) prevention

Abstract

In the 1970s and 1980s, GVHD prevention approaches were limited in number. Recent advances in our understanding of the requirements for T-cell immune responses and for basic mechanism(s) involved in GVHD pathophysiology have led to exciting new strategies for GVHD prevention. This review focuses upon recent developments in GVHD prevention generated over the past 5 years. We have selected five different types of strategies to highlight including: 1) the in vivo targeting of GVHD-reactive T cells using either intact and F(ab')2 fragments of monoclonal antibodies directed against T-cell-surface determinants or immunotoxins which consist of antibodies linked to toxins, 2) a comparison of the in vivo immunosuppressive effects of FK506 and rapamycin on T-cell signaling, 3) the inhibition of T-cell activation through blockade of costimulatory or adhesogenic signals, 4) shifting the balance between acute GVHD-inducing T-helper-type 1 (Th1) T cells to anti-inflammatory T-helper-type 2 (Th2)-type T cells, and 5) the regulation of alloreactive T-cell activation by treatment with peptide analogs which affect either TCR/MHC, CD4/MHC class II, or CD8/MHC class I interactions. Collectively, these approaches are illustratrative of the progress made in extending our GVHD prevention armamentarium.

IFN‐γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease

“…One of the strategies cited for control and/or prevention of GVHD has been to induce a shift from Th1 to Th2 cytokines [60]. As IFN-c is a known stimulant of Th1 cytokine production, a potential harmful side effect from IFN-c-stimulated MSC treatment might be the release Th1 cytokines, IL-2, GM-CSF, and TNF-a [61].…”

Cytokine expression during acute graft-versus-host disease after allogeneic peripheral stem cell transplantation

“…Acute graft-versus-host disease (aGVHD) is the major complication of patients who receive allogeneic grafts. 1 It is now well established that mature T cells present in grafts initiate the aGVHD reaction when they are activated by the host major or minor alloantigens. Indeed, depletion of the T cells in graft reduced the incidence of aGVHD, but increased the rate of relapse, providing evidence of the role of donor-type T cells in the graft-versus-leukemia effect.…”

Th1/Th2 cytokine profiles and their relationship to clinical features in patients following nonmyeloablative allogeneic stem cell transplantation

“…The Th1/Th2 polarization of T helper cell subsets may play an important role in the development of aGVHD [8]. In both mice and humans, a ''cytokine storm'' related to the Th1 phenotype has been found to correlate with the development of GVHD [9,10].…”