CD4+TCRαβ+ T-cells developing after allogeneic bone marrow transplantation in patients with chronic myelogenous leukaemia. Dipyridamole inhibits functionally heterogeneous T-cell clones

Abstract We evaluated T-cell mediated lymphokine activated killer (LAK) function during the late (greater than 5 months) reconstitution phase after T cell-depleted allogeneic bone marrow transplantation (BMT) for hematologic malignancy. Since LAK cells are sustained by interleukin-2 (IL-2), we also investigated the ability of post-BMT T cells to produce IL-2. These functions were investigated at the clonal level. More than 200 T-cell clones from six long-term BMT recipients were generated and compared with 60 T-cell clones derived from two normal controls. Almost all the CD8+ clonal cultures from BMT recipients expressed cytolytic activity in a lectin-dependent cellular cytoxicity assay. Interestingly, a higher proportion of BMT recipient-derived cytolytic clones were able to mediate LAK activity in comparison with control clones (28% versus 4%, P less than .05). However, T-cell clones from BMT recipients, as opposed to control clones, were largely incapable of producing IL-2. Given the high proportions of post-BMT circulating CD8+ T cells, it appears that, in long-term BMT recipients, the precursors of nonspecific LAK effectors are present at above normal levels. However, their function may be defective in vivo due to poor IL-2 production.

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Cytolytic function of clonable T cells after human bone marrow transplantation

Blood ◽

10.1182/blood.v75.6.1364.bloodjournal7561364 ◽

1990 ◽

Vol 75 (6) ◽

pp. 1364-1369

Author(s):

A Velardi ◽

P Varese ◽

CE Grossi ◽

N Albi ◽

C Dembech ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Bone Marrow Transplantation ◽

T Cell ◽

Marrow Transplantation ◽

Allogeneic Bone Marrow Transplantation ◽

Allogeneic Bone ◽

T Cell Clones ◽

Cell Clones

We evaluated T-cell mediated lymphokine activated killer (LAK) function during the late (greater than 5 months) reconstitution phase after T cell-depleted allogeneic bone marrow transplantation (BMT) for hematologic malignancy. Since LAK cells are sustained by interleukin-2 (IL-2), we also investigated the ability of post-BMT T cells to produce IL-2. These functions were investigated at the clonal level. More than 200 T-cell clones from six long-term BMT recipients were generated and compared with 60 T-cell clones derived from two normal controls. Almost all the CD8+ clonal cultures from BMT recipients expressed cytolytic activity in a lectin-dependent cellular cytoxicity assay. Interestingly, a higher proportion of BMT recipient-derived cytolytic clones were able to mediate LAK activity in comparison with control clones (28% versus 4%, P less than .05). However, T-cell clones from BMT recipients, as opposed to control clones, were largely incapable of producing IL-2. Given the high proportions of post-BMT circulating CD8+ T cells, it appears that, in long-term BMT recipients, the precursors of nonspecific LAK effectors are present at above normal levels. However, their function may be defective in vivo due to poor IL-2 production.

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Transmission of psoriatic arthritis by allogeneic bone marrow transplantation for chronic myelogenous leukaemia from an HLA-identical donor

Rheumatology ◽

10.1093/rheumatology/38.1.89 ◽

1999 ◽

Vol 38 (1) ◽

pp. 89-90 ◽

Cited By ~ 18

Author(s):

T. Daikeler ◽

I. Gunaydin ◽

H. Einsele ◽

L. Kanz ◽

I. Kotter

Keyword(s):

Bone Marrow ◽

Psoriatic Arthritis ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Chronic Myelogenous Leukaemia ◽

Allogeneic Bone Marrow Transplantation ◽

Myelogenous Leukaemia ◽

Allogeneic Bone Marrow ◽

Allogeneic Bone

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

Blood ◽

10.1182/blood.v71.5.1196.1196 ◽

1988 ◽

Vol 71 (5) ◽

pp. 1196-1200 ◽

Cited By ~ 31

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./

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T-Cell Immune Reconstitution in Pediatric Leukemia Patients After Allogeneic Bone Marrow Transplantation With T-Cell–Depleted or Unmanipulated Grafts: Evaluation of Overall and Antigen-Specific T-Cell Repertoires

Blood ◽

10.1182/blood.v94.12.4358.424k02_4358_4369 ◽

1999 ◽

Vol 94 (12) ◽

pp. 4358-4369 ◽

Cited By ~ 2

Author(s):

Barbara C. Godthelp ◽

Maarten J.D. van Tol ◽

Jaak M. Vossen ◽

Peter J. van den Elsen

Keyword(s):

Bone Marrow ◽

T Cells ◽

Bone Marrow Transplantation ◽

T Cell ◽

Marrow Transplantation ◽

Immune Reconstitution ◽

Allogeneic Bone Marrow Transplantation ◽

Cell Selection ◽

Allogeneic Bone ◽

T Cell Selection

To evaluate the role of T-cell selection in the thymus and/or periphery in T-cell immune reconstitution after allogeneic bone marrow transplantation (allo-BMT), we have analyzed the overall and antigen-specific T-cell repertoires in pediatric allo-BMT recipients treated for leukemia. We observed a lack of overall T-cell receptor (TCR) diversity in the repopulating T cells at 3 months after allo-BMT, as was deduced from complementarity determining region 3 (CDR3) size distribution patterns displaying reduced complexity. This was noted particularly in recipients of a T-cell–depleted (TCD) graft and, to a lesser extent, also in recipients of unmanipulated grafts. At 1 year after allo-BMT, normalization was observed of TCR CDR3 size complexity in almost all recipients. Analysis of the antigen-specific T-cell repertoire at 1 year after BMT showed that the T cells responding to tetanus toxoid (TT) differed in TCR gene segment usage and in amino acid composition of the CDR3 region when comparing the recipient with the donor. Moreover, the TT-specific TCR repertoire was found to be stable within a given allo-BMT recipient, because TT-specific T cells with completely identical TCRs were found at 3 consecutive years after transplantation. These observations suggest an important role for T-cell selection processes in the complete restoration of the T-cell immune repertoire in children after allo-BMT.

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Donor T-cell alloreactivity against host thymic epithelium limits T-cell development after bone marrow transplantation

Blood ◽

10.1182/blood-2006-07-034157 ◽

2007 ◽

Vol 109 (9) ◽

pp. 4080-4088 ◽

Cited By ~ 58

Author(s):

Mathias M. Hauri-Hohl ◽

Marcel P. Keller ◽

Jason Gill ◽

Katrin Hafen ◽

Esther Pachlatko ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Bone Marrow Transplantation ◽

T Cell ◽

Marrow Transplantation ◽

Allogeneic Bone Marrow Transplantation ◽

Allogeneic Bone Marrow ◽

Thymic Epithelial Cells ◽

Allogeneic Bone ◽

Donor T Cells

Abstract Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell regeneration in recipients of allogeneic bone marrow transplants through yet to be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T cells home into the thymus of unconditioned recipients. There, activated donor T cells secrete IFN-γ, which in turn stimulates the programmed cell death of thymic epithelial cells (TECs). Because TECs themselves are competent and sufficient to prime naive allospecific T cells and to elicit their effector function, the elimination of host-type professional antigen-presenting cells (APCs) does not prevent donor T-cell activation and TEC apoptosis, thus precluding normal thymopoiesis in transplant recipients. Hence, strategies that protect TECs may be necessary to improve immune reconstitution following allogeneic bone marrow transplantation.

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