GANCICLOVIR-SENSITIVE ACUTE GRAFT-VERSUS-HOST DISEASE IN MICE RECEIVING HERPES SIMPLEX VIRUS-THYMIDINE KINASE???EXPRESSING DONOR T CELLS IN A BONE MARROW TRANSPLANTATION SETTING1

2000 ◽  
Vol 69 (4) ◽  
pp. 503-508 ◽  
Author(s):  
Emmanuel Contassot ◽  
Christophe Ferrand ◽  
R??gis Angonin ◽  
Jos?? L. Cohen ◽  
Marcelo de Carvalho Bittencourt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Herpes Simplex Virus ◽  
Bone Marrow Transplantation ◽  
Herpes Simplex ◽  
Graft Versus Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells ◽  
Simplex Virus ◽  
Acute Graft

Monitoring of Developing Graft-Versus-Host Disease Mediated by Herpes Simplex Virus Thymidine Kinase Gene-Transduced T Cells

2003 ◽  
Vol 14 (4) ◽  
pp. 341-351 ◽  
Author(s):  
Sebastianus Kolen ◽  
Mo Weijtens ◽  
Anton Hagenbeek ◽  
Anke van Spronsen ◽  
Saskia Smulders ◽  
...  
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Graft Versus Host Disease ◽  
Thymidine Kinase Gene ◽  
Kinase Gene ◽  
Host Disease ◽  
Graft Versus Host ◽  
Simplex Virus

scholarly journals Impact of pretransplant conditioning and donor T cells on chimerism, graft-versus-host disease, graft-versus-leukemia reactivity, and tolerance after bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2515-2523
Author(s):  
RL Truitt ◽  
AA Atasoylu
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Mixed Chimerism ◽  
Cell Content ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
Donor T Cells

Graft rejection, mixed chimerism, graft-versus-host disease (GVHD), leukemia relapse, and tolerance are interrelated manifestations of immunologic reactivity between donor and host cells that significantly affect survival after allogeneic bone marrow transplantation (BMT). In this report, a mouse model of BMT, in which the donor and host were compatible at the major histocompatibility complex (MHC), was used (1) to examine the interrelationship of pretransplant conditioning and T- cell content of donor BM with regard to lymphoid chimerism and GVHD and (2) to determine how these factors affected graft-versus-leukemia (GVL) reactivity and donor-host-tolerance. AKR (H-2k) host mice were administered optimal or suboptimal total body irradiation (TBI) as pretransplant conditioning followed by administration of BM cells from B10.BR (H-2k) donor mice with or without added spleen cells as a source of T lymphocytes. Transplanted mice were injected with a supralethal dose of AKR leukemia cells 20 and 45 days post-BMT to assess GVL reactivity in vivo. The pretransplant conditioning of the host and T- cell content of the donor marrow affected the extent of donor T-cell chimerism and the severity of GVH disease. GVL reactivity was dependent on transplantation of mature donor T cells and occurred only in complete chimeras. Transplantation of T-cell-deficient BM resulted in the persistence of host T cells, ie, incomplete donor T-cell chimerism, even when lethal TBI was used. Mixed chimerism was associated with a lack of GVL reactivity, despite the fact that similar numbers of donor T cells were present in the spleens of mixed and complete chimeras. In this model, moderate numbers of donor T cells facilitated complete donor T-cell engraftment, caused only mild GVHD, and provided a significant GVL effect without preventing the subsequent development of tolerance after conditioning with suboptimal TBI. In contrast, severe, often lethal, GVHD developed when the dose of TBI was increased, whereas tolerance and no GVH/GVL reactivity developed when the T-cell content of the marrow was decreased.

scholarly journals T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1416-1423 ◽  
Author(s):  
JW Gratama ◽  
A Naipal ◽  
P Oljans ◽  
FE Zwaan ◽  
LF Verdonck ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Acute Graft

Abstract Acute graft-versus-host disease (GVHD), a major complication of allogeneic bone marrow transplantation (BMT), is probably mediated by T lymphocytes present in the marrow graft. In this study, the repopulation of the peripheral blood with T4+ and T8+ T cells was investigated during the period preceding the occurrence of acute GVHD. Twenty-four allogeneic and 11 autologous BMT recipients were monitored from day 4 post-BMT onward by the use of monoclonal antibodies, indirect immunofluorescence, and flow cytometry. The recipients of allogeneic transplants received methotrexate as GVHD prophylaxis. Similar recovery patterns for T4+ and T8+ T cells were found following autologous and allogeneic BMT. However, lymphoid repopulation occurred at a clearly faster rate after autologous BMT. T4+ T cells were the first to reappear in the peripheral blood, followed by T8+ T cells 4–7 days later. The T8+ T cell reconstitution occurred at an even faster rate in patients who were to develop grade II-IV GVHD, as compared with those with grade O-I GVHD, thus leading to an earlier decrease in the T4/T8 ratio. Of 10 patients with a T4/T8 ratio less than 2.5 at day 19, 9 developed grade II-IV GVHD and 1 showed no GVHD. Of 14 patients with a ratio greater than 2.5 at that time, only 2 developed grade II-IV and 12 grade O-I GVHD (p less than 0.001). In the 11 patients developing grade II-IV GVHD, the T4/T8 ratio decreased to values less than 2.5 before the first clinical symptoms of GVHD in 9; it coincided in one and occurred later in another patient. Thus, early monitoring of the T4/T8 ratio can distinguish patients at risk of developing grade II-IV GVHD.

scholarly journals T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1416-1423 ◽  
Author(s):  
JW Gratama ◽  
A Naipal ◽  
P Oljans ◽  
FE Zwaan ◽  
LF Verdonck ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Acute Graft

Acute graft-versus-host disease (GVHD), a major complication of allogeneic bone marrow transplantation (BMT), is probably mediated by T lymphocytes present in the marrow graft. In this study, the repopulation of the peripheral blood with T4+ and T8+ T cells was investigated during the period preceding the occurrence of acute GVHD. Twenty-four allogeneic and 11 autologous BMT recipients were monitored from day 4 post-BMT onward by the use of monoclonal antibodies, indirect immunofluorescence, and flow cytometry. The recipients of allogeneic transplants received methotrexate as GVHD prophylaxis. Similar recovery patterns for T4+ and T8+ T cells were found following autologous and allogeneic BMT. However, lymphoid repopulation occurred at a clearly faster rate after autologous BMT. T4+ T cells were the first to reappear in the peripheral blood, followed by T8+ T cells 4–7 days later. The T8+ T cell reconstitution occurred at an even faster rate in patients who were to develop grade II-IV GVHD, as compared with those with grade O-I GVHD, thus leading to an earlier decrease in the T4/T8 ratio. Of 10 patients with a T4/T8 ratio less than 2.5 at day 19, 9 developed grade II-IV GVHD and 1 showed no GVHD. Of 14 patients with a ratio greater than 2.5 at that time, only 2 developed grade II-IV and 12 grade O-I GVHD (p less than 0.001). In the 11 patients developing grade II-IV GVHD, the T4/T8 ratio decreased to values less than 2.5 before the first clinical symptoms of GVHD in 9; it coincided in one and occurred later in another patient. Thus, early monitoring of the T4/T8 ratio can distinguish patients at risk of developing grade II-IV GVHD.

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