scholarly journals Essential Role of the Thymus to Reconstitute Naive (CD45RA+) T-Helper Cells After Human Allogeneic Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 850-857 ◽  
Author(s):  
Andreas Heitger ◽  
Nikolaus Neu ◽  
Hannelore Kern ◽  
Eva-Renate Panzer-Grümayer ◽  
Hildegard Greinix ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Helper Cells ◽  
Marrow Transplantation ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
T Helper ◽  
Cd4 Cells ◽  
Helper Cells

To contribute to the understanding of the role of the thymus in humans in the reconstitution of naive (CD45RA+) T cells after bone marrow transplantation (BMT), we compared T-cell regeneration in a unique situation, namely a thymectomized cancer patient (15 years old), with that of thymus-bearing patients after allogeneic BMT. These cases shared features of transplantation (total body irradiation, HLA-matched donors, and graft-versus-host disease prophylaxis with cyclosporine A) and all had an uncomplicated posttransplantation course. As shown by fluorescence-activated cell sorting analyses, the thymectomized host failed to reconstitute CD45RA+ T-helper cells even 24 months after BMT (11% CD45RA+ of CD4+ cells). In this patient, preferentially CD45RO+ cells contributed to the recovery of CD4+ cells (206 of 261/μL at 6 months and 463 of 558/μL at 24 months after BMT, CD45RA+ of CD4+ cells), whereas CD45RA+ cells remained low (<60/μL). In contrast, nine thymus-bearing hosts (5 children and 4 adults) examined between 6 and 24 months after BMT effectively reconstituted CD4+/CD45RA+ cells according to their normal age-related range (≥28% in adults and ≥50% in children). Five of these were analyzed sequentially at 6 and 9 months after BMT. Within this period, CD45RA+ cells increasingly contributed to the recovery of CD4+ cells (median, +21%), even when total CD4+ cells decreased. With respect to T-cytotoxic/suppressor cells, the thymectomized host retained the capacity to recover CD45RA+ cells (137 of 333/μL at 6 months and 596 of 1,046/μL at 24 months after BMT, CD45RA+ of CD8+ cells), a proportion similar to that seen in thymus-bearing hosts. These findings suggest that a thymus-independent pathway exists to regenerate CD45RA+ T-cytotoxic/suppressor cells, but residual thymus is essential to reconstitute naive (CD45RA+) T-helper cells after BMT in humans.

scholarly journals Essential Role of the Thymus to Reconstitute Naive (CD45RA+) T-Helper Cells After Human Allogeneic Bone Marrow Transplantation

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 850-857 ◽  
Author(s):  
Andreas Heitger ◽  
Nikolaus Neu ◽  
Hannelore Kern ◽  
Eva-Renate Panzer-Grümayer ◽  
Hildegard Greinix ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Helper Cells ◽  
Marrow Transplantation ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
T Helper ◽  
Cd4 Cells ◽  
Helper Cells

Abstract To contribute to the understanding of the role of the thymus in humans in the reconstitution of naive (CD45RA+) T cells after bone marrow transplantation (BMT), we compared T-cell regeneration in a unique situation, namely a thymectomized cancer patient (15 years old), with that of thymus-bearing patients after allogeneic BMT. These cases shared features of transplantation (total body irradiation, HLA-matched donors, and graft-versus-host disease prophylaxis with cyclosporine A) and all had an uncomplicated posttransplantation course. As shown by fluorescence-activated cell sorting analyses, the thymectomized host failed to reconstitute CD45RA+ T-helper cells even 24 months after BMT (11% CD45RA+ of CD4+ cells). In this patient, preferentially CD45RO+ cells contributed to the recovery of CD4+ cells (206 of 261/μL at 6 months and 463 of 558/μL at 24 months after BMT, CD45RA+ of CD4+ cells), whereas CD45RA+ cells remained low (&lt;60/μL). In contrast, nine thymus-bearing hosts (5 children and 4 adults) examined between 6 and 24 months after BMT effectively reconstituted CD4+/CD45RA+ cells according to their normal age-related range (≥28% in adults and ≥50% in children). Five of these were analyzed sequentially at 6 and 9 months after BMT. Within this period, CD45RA+ cells increasingly contributed to the recovery of CD4+ cells (median, +21%), even when total CD4+ cells decreased. With respect to T-cytotoxic/suppressor cells, the thymectomized host retained the capacity to recover CD45RA+ cells (137 of 333/μL at 6 months and 596 of 1,046/μL at 24 months after BMT, CD45RA+ of CD8+ cells), a proportion similar to that seen in thymus-bearing hosts. These findings suggest that a thymus-independent pathway exists to regenerate CD45RA+ T-cytotoxic/suppressor cells, but residual thymus is essential to reconstitute naive (CD45RA+) T-helper cells after BMT in humans.

scholarly journals Imbalances within the peripheral blood T-helper (CD4+) and T-suppressor (CD8+) cell populations in the reconstitution phase after human bone marrow transplantation

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1196-1200 ◽  
Author(s):  
A Velardi ◽  
A Terenzi ◽  
S Cucciaioni ◽  
R Millo ◽  
CE Grossi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
T Cell Subsets ◽  
Allogeneic Bone ◽  
T Helper

Abstract Peripheral blood T cell subsets were evaluated in 11 patients during the reconstitution phase after allogeneic bone marrow transplantation and compared with 11 age-matched controls. The proportion of cells coexpressing Leu7 and CD11b (C3bi receptor) markers was determined within the CD4+ (T-helper) and the CD8+ (T-suppressor) subsets by two- color immunofluorescence analysis. CD4+ and CD8+ T cells reached normal or near-normal values within the first year posttransplant. In contrast to normal controls, however, most of the cells in both subsets coexpressed the Leu7 and CD11b markers. T cells with such phenotype display the morphological features of granular lymphocytes (GLs) and a functional inability to produce interleukin 2 (IL 2). These T cell imbalances were not related to graft v host disease (GvHD) or to clinically detectable virus infections and may account for some defects of cellular and humoral immunity that occur after bone marrow transplantation./

Dynamic Changes and Impact of Myeloid Derived Suppressor Cells in Allogeneic Bone Marrow Transplantation in Mice.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2999-2999
Author(s):  
Dapeng Wang ◽  
Yu Yu ◽  
Kenrick M Semple ◽  
Kelley M.K. Haarberg ◽  
Jianing Fu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Suppressor Cells ◽  
Allogeneic Bone ◽  
Myeloid Derived Suppressor Cells ◽  
Dynamic Changes ◽  
Tumor Relapse ◽  
Allogeneic Bmt

Abstract Abstract 2999 Myeloid-derived suppressor cells (MDSCs) are a group of myeloid cells comprised of hematopoietic progenitor cells and immature macrophages, dendritic cells and granulocytes. MDSCs accumulate in inflammatory diseases and various cancers. In this study, we investigated the dynamic changes and effects of MDSCs in graft-versus-host disease (GVHD) development and/or tumor relapse after allogeneic bone marrow transplantation (BMT). Using murine models of syngeneic and allogeneic BMT, we found that MDSCs transiently accumulated in the blood and spleen of recipients, but returned to the physiological levels shortly after BMT without GVHD. On the contrary, the levels of blood MDSCs always elevated after BMT with GVHD in the recipients of allogeneic BM+T cells. The MDSC accumulation was positively related with the severity of GVHD. In addition, MDSC accumulation was further increased upon tumor relapse. Although MDSCs isolated from both syngeneic and allogeneic BMT recipients inhibited T-cell proliferation under allogeneic stimulation ex vivo, MSDCs from GVHD recipients were significantly much suppressive compared to recipients without GVHD. Moreover, adding functional MDSCs in donor graft alleviated GVHD, whereas partial depletion of MDSCs in vivo using all-trans retinoic acid exacerbated GVHD(Figure 1A and B). These results indicate MDSCs may serve as a biomarker for acute GVHD and tumor relapse after allogeneic BMT. The accumulated MDSCs are not sufficient to completely prevent GVHD although they do ameliorate GVHD. Hence, manipulating MDSCs could be implicated in allogeneic BMT for controlling GVHD or tumor relapse. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

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