Correlation of peripheral blood OX40+(CD134+) T cells with chronic graft-versus-host disease in patients who underwent allogeneic hematopoietic stem cell transplantation

Kotani, Ai; Ishikawa, Takayuki; Matsumura, Yasuhiro; Ichinohe, Tatsuo; Ohno, Hitoshi; Hori, Tomohide; Uchiyama, Takashi

doi:10.1182/blood.v98.10.3162

Cited by 45 publications

(29 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ϩ and CD4 ϩ T cells in SLE (43) and in chronic graftvs-host disease (44). The expression of CD134 may directly contribute to activation of type 2 cells.…”

Section: Cd45rcmentioning

confidence: 99%

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Field

Caccavelli

Bloch

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Exposure of newborn animals to a foreign Ag may result in immunological tolerance to that specific Ag, a phenomenon called neonatal tolerance. We have previously reported that neonatal administration to Brown-Norway rats of mercury, a heavy metal toxicant, induces a dominant tolerance, specific for the chemical otherwise responsible for Th2 cell-mediated autoimmune responses in this susceptible strain of rats. Neonatal exposure to Ags can prime immunity, rather than inactivate or delete responses, and sustain regulatory functions effective against autoreactive T cells. Here, we address whether such a tolerant response is due to the generation of regulatory cells. The results suggest that the CD8+ T cell subset is involved in neonatal tolerance to mercuric salt-induced Th2 autoimmune disease. Thus, we demonstrate that in vivo CD8 depletion breaks tolerance following mercury recall in animals under a neonatal tolerance protocol. Furthermore, adoptive cotransfer of splenocytes from naive and tolerant rats as well as transfer of CD8+ T cells from tolerant animals prevent naive syngeneic rats from developing pathologic Th2 immune responses. These observations indicate that CD8+ T cells are endowed with regulatory functions in neonatal tolerance and mediate active suppression. Moreover, neonatal tolerance induced the expansion of CD8+CD45RChigh T cells and the emergence of a high percentage of IFN-γ-synthesizing CD8+ T cells, which probably reflects the implication of regulatory Tc1 cells. Thus, in vivo induction of neonatal tolerance suppresses Th2 autoimmune responses via generation of a CD8+ cell-mediated regulatory response.

show abstract

“…ϩ and CD4 ϩ T cells in SLE (43) and in chronic graftvs-host disease (44). The expression of CD134 may directly contribute to activation of type 2 cells.…”

Section: Cd45rcmentioning

confidence: 99%

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Field

Caccavelli

Bloch

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Modulation of the OX40-OX40L pathway potently ameliorates autoimmune-like diseases, such as experimental autoimmune encephalomyelitis (12), graft-versus-host disease (13), asthma (10), and arthritis (14). We have previously linked increased levels of cholesterol to upregulation of OX40 expression on T cells and showed that interruption of the OX40-OX40L interaction using an OX40L-blocking Ab leads to a reduction in the initiation of atherosclerosis (15).…”

mentioning

confidence: 99%

Interruption of the OX40–OX40 Ligand Pathway in LDL Receptor–Deficient Mice Causes Regression of Atherosclerosis

Foks

Puijvelde

Bot

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Patients suffering from cardiovascular disease have well-established atherosclerotic lesions, rendering lesion regression of therapeutic interest. The OX40 (TNFRSF4)–OX40 ligand (OX40L; TNFSF4) pathway is important for the proliferation and survival of T cells, stimulates B cells, and is associated with cardiovascular disease. We hypothesized that interference with the OX40–OX40L pathway, in combination with decreases in cholesterol, may induce regression of atherosclerosis. LDLr−/− mice were fed a Western-type diet for 10 wk, after which they received chow diet and were treated with anti-OX40L or PBS for 10 wk. A significant regression of lesions was observed in the aorta and aortic arch of anti-OX40L–treated mice compared with control mice. Interference of the OX40–OX40L pathway reduced Th2 responses, as shown by decreases in GATA-3 and IL-4 levels. Also, IgE levels were decreased, as demonstrated by reduced mast cell presence and activation. Notably, IL-5 production by T and B1 cells was increased, thus enhancing atheroprotective oxidized low-density lipoprotein–specific IgM production. The increase in IL-5 production and IgM was mediated by IL-33 production by APCs upon OX40L blockade. We conclude that interruption of the OX40–OX40L signaling pathway, combined with decreases in dietary cholesterol, induces the regression of atherosclerosis through induction of IL-5–producing T cells and oxidized low-density lipoprotein–specific IgM and reductions in Th2 and mast cells.

show abstract

“…31,58,59 In humans, OX-40 (CD134, a member of TNF receptor superfamily responsible for costimulation) expressing CD4 ϩ cells are reportedly associated with onset of chronic GVHD and decreased response to initial therapy. 60 If OX-40 is a marker of cells involved in chronic GVHD, then targeting these cells or their interactions at the onset of chronic GVHD may be therapeutic. In mice, antibody to the OX-40 ligand (OX-40L) decreases acute GVHD, but to this point, human trials have not been conducted.…”

mentioning

confidence: 99%

New approaches for preventing and treating chronic graft-versus-host disease

Lee

2005

Blood

127

View full text Add to dashboard Cite

Despite improvements in the practice of allogeneic hematopoietic stem cell transplantation (HCT) over the last 25 years, chronic graft-versus-host disease (GVHD) remains a substantial problem with little change in the incidence, morbidity, and mortality of this complication. In fact, with increased use of peripheral blood, transplantation of older patients, and less immediate transplantation-related mortality, the prevalence of chronic GVHD may increase. One of the difficulties in combating chronic GVHD is a lack of understanding about the pathophysiology of the syndrome. IntroductionChronic graft-versus-host disease (GVHD) is the most serious and common long-term complication of allogeneic hematopoietic stem cell transplantation (HCT), occurring in 20% to 70% of people surviving more than 100 days. 1,2 Approximately half of affected people have 3 or more involved organs, and treatment typically requires immunosuppressive medications for a median of 1 to 3 years. Because of higher treatment-related (nonrelapse) mortality, chronic GVHD remains the major cause of late death despite its association with a lower relapse rate. 3,4 In addition, secondary malignancies are more common in people with chronic GVHD, particularly of commonly involved tissues such as mouth and skin, suggesting that chronic inflammation, prolonged exposure to immunosuppressive medications, or immune dysregulation facilitates the development of new cancers. 5 Finally, the functional consequences of chronic GVHD organ involvement are major determinants of the health and quality of life of survivors. 6,7 Despite the well-recognized adverse effects of chronic GVHD on the long-term success of allogeneic transplantation, its pathophysiology is poorly understood, and management strategies beyond systemic corticosteroids have not been established.While there are some lessons that can be translated from basic and clinical studies of acute GVHD, several lines of evidence suggest that chronic GVHD is not simply a continuation of acute GVHD, and that separate approaches will be required for its prevention and management. First, except for T-cell depletion and use of umbilical cord blood, the major innovations that have improved acute GVHD rates do not seem to have affected chronic GVHD incidence. Second, while there is significant overlap between the organs involved in acute and chronic GVHD, the distribution of affected organs in chronic GVHD is much broader. Fully evolved chronic GVHD is largely an inflammatory and fibrotic process, while acute GVHD is more likely to reflect apoptosis and necrosis. Although traditionally the boundary between acute and chronic GVHD has been set at 100 days after transplantation, more recent definitions hinge on different clinical manifestations rather than time of onset. Third, while acute GVHD is highly associated with subsequent chronic GVHD, approximately 25% to 35% of chronic GVHD is de novo without any preceding acute manifestations, while 20% to 30% of people who had acute GVHD do not go on to develop chronic GVH...

show abstract

Correlation of peripheral blood OX40+(CD134+) T cells with chronic graft-versus-host disease in patients who underwent allogeneic hematopoietic stem cell transplantation

Cited by 45 publications

References 18 publications

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Interruption of the OX40–OX40 Ligand Pathway in LDL Receptor–Deficient Mice Causes Regression of Atherosclerosis

New approaches for preventing and treating chronic graft-versus-host disease

Contact Info

Product

Resources

About