CD4+CD25+ regulatory T cells in human hematopoietic cell transplantation

Zorn, Emmanuel

doi:10.1016/j.semcancer.2005.11.008

Cited by 35 publications

(25 citation statements)

References 75 publications

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“…Primarily because of their effects in controlling autoimmunity and therefore GvHD after HSCT, application of ex vivo expanded regulatory T cells seems to be a promising therapeutic approach to achieve a modulation of effector T cells and thus prevention from GvHD. 39,40 On the other hand, chronic GvHD and its treatment were reported to influence immune reconstitution. In this context, an impaired reconstitution of B cells was noted in case of extensive chronic GvHD.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Heining

Spyridonidis

Bernhardt

et al. 2007

Bone Marrow Transplant

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Here we investigated the influence of parameters known before hematopoietic stem cell transplantation (HSCT) as well as the relevance of graft-versus-host disease (GvHD) and cytomegalovirus (CMV) reactivation on post transplant lymphocyte reconstitution in 148 patients treated in our institution between 1996 and 2003. Median patient age was 42 (19-68) years, HSCT followed standard high dose (n ¼ 91) or reduced-intensity conditioning regimens (n ¼ 57) with bone marrow (BM, n ¼ 67) or peripheral blood stem cells (PBSC, n ¼ 81) from related (n ¼ 71) or unrelated (n ¼ 77) donors. In the first months, we observed a partially faster reconstitution of CD3 þ 4 þ , CD3 þ 8 þ and CD4 þ 45RA þ T cells in patients following peripheral blood stem cell transplantation when compared to bone marrow transplantation. Prolonged CD3 þ 4 þ and CD4 þ 45RA þ lymphopenia was noted after unrelated donor HSCT and GvHD prophylaxis containing anti-T-lymphocyte globulin. Lymphocyte subset counts in patients older than the median age were comparable to those in patients transplanted at a younger age and not influenced by the conditioning regimen. CD3 þ 8 þ T cell reconstitution was strongly correlated with CMV reactivation, but not significantly affected by CMV serostatus before HSCT. Incidence or extent of GvHD did not significantly influence lymphocyte reconstitution. Therefore, the source of graft is the most predictive parameter in early lymphocyte reconstitution, but the differences in lymphocyte recovery completely resolved within the first year after HSCT.

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Section: Discussionmentioning

confidence: 99%

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Heining

Spyridonidis

Bernhardt

et al. 2007

Bone Marrow Transplant

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“…For the advances in expansion of auto-and alloantigen-specific Treg for future therapy please refer to recent reviews [41,42].…”

Section: Manipulation Of Treg For Cancer Therapymentioning

confidence: 99%

FOXP3⁺ regulatory T cells: Current controversies and future perspectives

2006

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Regulatory T cells (Treg) provide protection from autoimmune disease, graft‐versus‐host disease, transplant rejection and overwhelming tissue destruction during infections. Conversely, high Treg numbers enable cancer cells to evade the host immune response. Thus, Treg are seen as an important tool to manipulate the immune response. However, as the immunological community is trying to move this knowledge from mice to humans, contradictory results regarding the number and function of Treg in various diseases are appearing. This problem arises because we cannot clearly define Treg populations on the basis of expression of CD25 and other cell surface markers in humans. This review addresses the utility of the FOXP3 forkhead transcription factor for the identification of Treg populations and summarizes recent data on the expression of FOXP3 in lymphomas. It is crucial to really understand Treg biology before attempting therapies, including (i) the injection of expanded Treg to cure autoimmune disease or prevent graft‐versus‐host disease or (ii) the depletion or inhibition of Treg in cancer therapy. For instance, new data arising from the study of haematological malignancies highlight the additional complexity of systems where malignant cell populations may also be direct Treg targets.

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“…1 Impaired thymic function with defective immune reconstitution is considered the main cause of cGVHD, 2,3 although recent experimental and clinical data suggest that defects of peripheral immune regulation could play a key role as well. [4][5][6] Failure of both thymic function and peripheral regulation may induce hyperactivation of the immune system, with cytokine dysregulation, as in autoimmune diseases. [2][3][4][5][6][7][8] After Allo-SCT, the immune system may be unbalanced towards a Th1-type response.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study

Skert

Damiani

Michelutti

et al. 2009

Bone Marrow Transplant

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The role of different cytokines and cells of immune system in the pathogenesis of chronic GVHD (cGVHD) is still controversial. Earlier studies, which were either retrospective or analysed one or a few factors, did not show unequivocal results. We prospectively evaluated cytokine levels and lymphocyte subsets in 30 patients who underwent Allo-SCT to investigate their possible correlation with cGVHD. Levels of IL-4, IL-6, IL-10, IFN-c, tumour necrosis factor-alpha (TNF-a) and its soluble receptors were assessed by ELISA in 30 patients at different times after SCT. Lymphocyte subsets were evaluated by flow cytometry in peripheral blood at the same times as cytokines. A multivariate analysis was performed using principal component analysis and multi-factor ANOVA (analysis of variance). Eighteen patients developed cGVHD at a median time of 6 months (range, 5-9) after SCT. In multivariate analysis, we observed a correlation between cGVHD and clusters of cytokines and lymphocyte subsets from the third to the sixth month after SCT. These clusters changed their composition over time, but they constantly included natural killer (NK) and CD152 þ T cells as negative predictors of cGVHD. TNF-a prevailed among other cytokines before the onset of cGVHD. This prevalence could be related partly to the defect of immunoregulatory cells.

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CD4+CD25+ regulatory T cells in human hematopoietic cell transplantation

Cited by 35 publications

References 75 publications

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

FOXP3⁺ regulatory T cells: Current controversies and future perspectives

Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study

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CD4+CD25+ regulatory T cells in human hematopoietic cell transplantation

Cited by 35 publications

References 75 publications

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

FOXP3+ regulatory T cells: Current controversies and future perspectives

Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study

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FOXP3⁺ regulatory T cells: Current controversies and future perspectives