Epirestriction and a Specialized Subset of T Helper Cells Are Key Factors in the Regulation of T Suppressor 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 (<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.

Download Full-text

CFU-GEMM Infused Influences Immunologic Recovery in Children Older Than 7 years After Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.4483.4483 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4483-4483

Author(s):

Katarzyna Drabko ◽

Marta Choma ◽

Agnieszka Zaucha-Prazmo ◽

Beata Wojcik ◽

Dorota Winnicka ◽

...

Keyword(s):

Stem Cell ◽

T Helper Cells ◽

Suppressor Cells ◽

T Helper ◽

Hematopoietic Stem ◽

Cd34 Cells ◽

Group 2 ◽

Graft Quality ◽

T Suppressor Cells ◽

Group 1

Abstract Abstract 4483 Introduction Reconstitution of immunity is considered as one of the most important factors predicting outcome after hematopoietic stem cell transplantation (HSCT). Age of the recipient as well as graft quality reflect on this process however this influence is not completely understood yet. In this study we aimed to evaluate the influence of graft quality on recovery of lymphocyte subpopulation. Patients and Methods The total number of 63 patients who underwent allogeneic transplantation in one center between May 2002 and November 2008, were included into the study. Median age of the patient was 8,6 (range 0.2-18) yrs. Patients were divided into 2 age groups: group 1 (n=26) children age 0,2-7 and group 2 (n=37) children >7 yrs. In all cases quality of graft were assessed by counting WBC, CD34 cells and CFU-GEMM. 45 patients (21 in group 1 and 24 in group 2) were available for evaluation of immune reconstitution: in those patients the absolute number of lymphocytes CD3/CD19 (B) cells, CD3/CD4 (T helper) cell, CD3/CD8 (T suppressor) cells and CD3/CD16+56 (NK) cells were measured 3 and 6 months after transplantation. Results Younger children (group 1) received higher median number of transplanted nucleated cells (4.9×108 vs 2.5×108, p=0.008), CD34 cells (5.6×106 vs 2.1×106, p=0.02) and CFU-GEMM (2.25×104 vs 1.17×104, p=0.01) than older ones (group 2). No differences were found in absolute values of B, T-helper, T-suppressor and NK cells at 3 and 6 months after transplantation (Table 1). In older children (group 2), but not in younger ones, the number of GFU-GEMM transplanted negatively correlated with number of T-suppressor cells 3 months post HSCT (p<0,05; r=-0,7) and positively with number of T-helper cells 6 moths after HSCT (p<0,05; r=0,73). Conclusions Number of CFU-GEMM infused influences immunologic recovery in children older than 7 years after HSCT. Graft quality correlates with number of T-suppressor cells and T-helper cells during first 6 months after HSCT and these changes may contribute to post transplant complications. Supported by grant MNiSW of Poland N407 117 35 Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Type 1 T Helper Cells Induce the Accumulation of Myeloid-Derived Suppressor Cells in the Inflamed Tgfb1 Knockout Mouse Liver

Hepatology ◽

10.1002/hep.23841 ◽

2010 ◽

Vol 52 (4) ◽

pp. 1350-1359 ◽

Cited By ~ 60

Author(s):

James G. Cripps ◽

Jing Wang ◽

Ann Maria ◽

Ian Blumenthal ◽

James D. Gorham

Keyword(s):

T Helper Cells ◽

Knockout Mouse ◽

Mouse Liver ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

T Helper ◽

Helper Cells

Download Full-text

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

Blood ◽

10.1182/blood.v90.2.850.850_850_857 ◽

1997 ◽

Vol 90 (2) ◽

pp. 850-857 ◽

Cited By ~ 4

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.

Download Full-text