Influence of graft‐versus‐host disease prophylaxis on early T‐lymphocyte regeneration following allogeneic bone marrow transplantation

Gratama, Jan W.; Würsch, A. M.; Nissen, C; Gratwohl, Aloïs; D'Amaro, J; Gast, Gijsbert C. de; Rood, Jon J. van; Speck, B

doi:10.1111/j.1365-2141.1986.tb02939.x

Cited by 6 publications

(3 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunosuppressive therapies use to control GVHD can affect lymphocyte reconstitution. Cyclosporine A and methotrexate alter B cell differentiation and thymocytes and peripheral T cell survival by interfering with TCR signaling ( 7 , 25 , 26 ). Novel drugs used to control refractory cGVHD are tyrosine kinase inhibitors, which can interfere with TCR or IL-7 signaling to reduce lymphocyte activation with potential detrimental effects on T cell survival ( 27 – 29 ).…”

Section: Immune Reconstitution After Allogeneic-sct and Gvhdmentioning

confidence: 99%

Restoring T Cell Homeostasis After Allogeneic Stem Cell Transplantation; Principal Limitations and Future Challenges

et al. 2018

View full text Add to dashboard Cite

For several leukemia patients, allogeneic stem cell transplantation (allogeneic-SCT) is the unique therapeutic modality that could potentially cure their disease. Despite significant progress made in clinical management of allogeneic-SCT, acute graft-versus-host disease (aGVHD) and infectious complications remain the second and third cause of death after disease recurrence. Clinical options to restore immunocompetence after allogeneic-SCT are very limited as studies have raised awareness about the safety with regards to graft-versus-host disease (GVHD). Preclinical works are now focusing on strategies to improve thymic functions and to restore the peripheral niche that have been damaged by alloreactive T cells. In this mini review, we will provide a brief overview about the adverse effects of GVHD on the thymus and the peripheral niche and the resulting negative outcome on peripheral T cell homeostasis. Finally, we will discuss the potential relevance of coordinating our studies on thymic rejuvenation and improvement of the peripheral lymphoid niche to achieve optimal T cell regeneration in GVHD patients.

show abstract

Section: Immune Reconstitution After Allogeneic-sct and Gvhdmentioning

confidence: 99%

Restoring T Cell Homeostasis After Allogeneic Stem Cell Transplantation; Principal Limitations and Future Challenges

et al. 2018

View full text Add to dashboard Cite

show abstract

“…5 Other ways of monitoring and predicting acute GVHD have been proposed, such as the repopulation pattern of the T lymphocytes. 6 The rate of CD8 + T cell repopulation and the expression of T cell activation markers such as CD25 have been shown to predict GVHD in some patient cohorts. 7,8 CD134 (OX40) is a 50-kDa type I transmembrane protein that is expressed on activated CD4 + T lymphocytes and to a lesser extent on CD8 + T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Expression of T cell activation antigen CD134 (OX40) has no predictive value for the occurrence or response to therapy of acute graft-versus-host disease in partial T cell-depleted bone marrow transplantation

Gadisseur

Gratama

Lamers

et al. 1999

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:CD134 (OX40) is a member of the tumor necrosis factor family which is expressed by activated T lymphocytes. CD134 expression on T cells was monitored during the first 35 days post-transplant in 14 patients, receiving either an HLA-identical sibling bone marrow transplant (BMT), a matched unrelated transplant (MUD-BMT) or an autologous peripheral blood progenitor cell transplant (PBPCT). The sibling and unrelated grafts were partially depleted of T cells. CD134 expression on CD4 + T cells peaked between 7 and 14 days after BMT, with a mean peak value of 45% of CD4 + cells (range 26-70%) over all three patient groups. The observed pattern of CD4 + CD134 + expression, an increase during the first 2 weeks post-BMT followed by a gradual decline towards values of 15-40%, was similar in all groups. No difference in the kinetics of CD134 expression by CD4 + T cells was observed between the patients that did or did not develop graft-versus-host disease (GVHD), nor did the clinical effect of any treatment given for GVHD correlate with alterations in CD134 expression by CD4 + T cells. Absolute CD4 + ,CD134 + T cell numbers showed a more rapid increment after autologous PBPCT than after sibling or MUD transplants. We conclude that expression of CD134 + by CD4 + T lymphocytes cannot serve as a surrogate marker for allo-reactivity. CD134 + expression may reflect lymphocyte regeneration, rather than alloreactivity. Keywords: graft-versus-host disease; T cell; CD134 antigen; bone marrow transplantation; reconstitution Graft-versus-host disease (GVHD) is still a major and potentially lethal complication of allogeneic bone marrow transplantation (BMT). 1 It has been shown that GVHD is initiated by donor-derived, alloreactive cytotoxic T lymphocytes (CTLs, CD8 + ) and helper T lymphocytes (CD4 + ), which is then further amplified by elaboration of cytokines. 2,3 The 'cytokine storm' concept of GVHD is defined as an outpouring of endogenous cytokines resulting in an attack of various tissues by antigen-specific and non-specific effector leukocyte populations. 3,4 Acute GVHD is preferably diagnosed on the basis of clinical signs together with biochemical data (liver enzymes, bilirubin). 5 Other ways of monitoring and predicting acute GVHD have been proposed, such as the repopulation pattern of the T lymphocytes. 6 The rate of CD8 + T cell repopulation and the expression of T cell activation markers such as CD25 have been shown to predict GVHD in some patient cohorts. 7,8 CD134 (OX40) is a 50-kDa type I transmembrane protein that is expressed on activated CD4 + T lymphocytes and to a lesser extent on CD8 + T lymphocytes. 9 It is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family. CD134 is rarely expressed by lymphocytes under normal conditions and, if it is, mainly by T lymphocytes residing in the lymph nodes. The ligand (L) for CD134 is a gp34 membrane bound protein, structurally similar to other ligands in the TNF receptor family with a still incompletely documented tissue distribution (activated B...

show abstract

“…All UCBT recipients receive GvHD prophylaxis (typically cyclosporine A and/or methotrexate and methylprednisolone). However, although efficient at preventing GvHD, these pharmaceutical agents impair the functional reconstitution of T cells and may have an impact on engraftment and on the incidence of OIs and leukemic relapse [108,109]. In the first 100 days posttransplant, incidence and severity of acute GvHD are lower in pediatric UCBT recipients as compared with recipients of HSCT from unrelated donors, in spite of higher levels of HLA mismatch in UCBT [5,110,111].…”

Section: Involvement Of T and Nk Cells In Gvhdmentioning

confidence: 99%

Complementary and contrasting roles of NK cells and T cells in pediatric umbilical cord blood transplantation

Mérindol

Charrier²,

Duval³

et al. 2011

Journal of Leukocyte Biology

View full text Add to dashboard Cite

UCBT has been used for almost 25 years to treat a variety of malignant and nonmalignant childhood diseases. The biological properties of NK cells and T cells and their implication in engraftment, immune reconstitution, OIs, leukemic relapse, and GvHD have been explored in the context of UCBT. These studies have established that lymphocytes have a major impact on the outcome of UCBT and that NK cells and T cells play complementary and contrasting roles in immune reconstitution and the GvL effect. Therefore, novel strategies to improve the outcome of UCBT recipients, including immunotherapeutic regimens, should be based on key immunologic features of UCB T lymphocytes and NK cells.

show abstract

Influence of graft‐versus‐host disease prophylaxis on early T‐lymphocyte regeneration following allogeneic bone marrow transplantation

Cited by 6 publications

References 23 publications

Restoring T Cell Homeostasis After Allogeneic Stem Cell Transplantation; Principal Limitations and Future Challenges

Restoring T Cell Homeostasis After Allogeneic Stem Cell Transplantation; Principal Limitations and Future Challenges

Expression of T cell activation antigen CD134 (OX40) has no predictive value for the occurrence or response to therapy of acute graft-versus-host disease in partial T cell-depleted bone marrow transplantation

Complementary and contrasting roles of NK cells and T cells in pediatric umbilical cord blood transplantation

Contact Info

Product

Resources

About