scholarly journals Quantitative assessment of posttransplant host-specific interleukin-2- secreting T-helper cell precursors in patients with and without acute graft-versus-host disease after allogeneic HLA-identical sibling bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 841-848 ◽  
Author(s):  
T Nierle ◽  
D Bunjes ◽  
R Arnold ◽  
H Heimpel ◽  
M Theobald
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Interleukin 2 ◽  
T Helper ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Acute Graft

Abstract Recent studies in mice and humans have emphasized an important contribution of host-reactive minor histocompatibility antigen (mH)- specific lymphokine-secreting donor T-helper cells (Th) for the induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). By using limiting dilution (LD) and clonal specificity analyses, we investigated in 14 patients with and without acute GVHD after non-T-depleted HLA-identical sibling BMT whether posttransplant host-reactive mH-specific interleukin-2 (IL-2)- secreting Th are involved in the development of clinically significant acute GVHD and the establishment of tolerance. At different time intervals posttransplant (I, days 0 through 45; II, days 45 through 90; III, days 90 through 180), host-specific IL-2-secreting Th-precursors (Th-p) were quantitatively assessed in six patients during clinically apparent grade II-III acute GVHD. Frequencies of responding Th-p ranged from 1/13,000 to 1 4,000. The presence of host-specific Th-p was significantly correlated with the development of grade II-III acute GVHD (P = .0003 by Fisher's exact test). The detectability of host- specific Th-p preceded the clinical onset of grade II-III acute GVHD. Host-specific Th-p were no longer detectable after the clinical resolution of grade II-III acute GVHD. No subsequent chronic GVHD was observed in these patients. However, prolonged occurrence of host- specific Th-p was accompanied by clinically persisting acute GVHD and the onset of secondary chronic GVHD. In patients with no acute GVHD (grade 0) (n = 7) and grade I (n = 1) acute GVHD, host-specific Th-p were not detectable at all. We conclude that host-reactive Th are critically involved in the development and maintenance of acute GVHD and may contribute to the establishment of tolerance after genotypically HLA-identical sibling BMT.

scholarly journals Quantitative assessment of posttransplant host-specific interleukin-2- secreting T-helper cell precursors in patients with and without acute graft-versus-host disease after allogeneic HLA-identical sibling bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 841-848
Author(s):  
T Nierle ◽  
D Bunjes ◽  
R Arnold ◽  
H Heimpel ◽  
M Theobald
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Interleukin 2 ◽  
T Helper ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Acute Graft

Recent studies in mice and humans have emphasized an important contribution of host-reactive minor histocompatibility antigen (mH)- specific lymphokine-secreting donor T-helper cells (Th) for the induction of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). By using limiting dilution (LD) and clonal specificity analyses, we investigated in 14 patients with and without acute GVHD after non-T-depleted HLA-identical sibling BMT whether posttransplant host-reactive mH-specific interleukin-2 (IL-2)- secreting Th are involved in the development of clinically significant acute GVHD and the establishment of tolerance. At different time intervals posttransplant (I, days 0 through 45; II, days 45 through 90; III, days 90 through 180), host-specific IL-2-secreting Th-precursors (Th-p) were quantitatively assessed in six patients during clinically apparent grade II-III acute GVHD. Frequencies of responding Th-p ranged from 1/13,000 to 1 4,000. The presence of host-specific Th-p was significantly correlated with the development of grade II-III acute GVHD (P = .0003 by Fisher's exact test). The detectability of host- specific Th-p preceded the clinical onset of grade II-III acute GVHD. Host-specific Th-p were no longer detectable after the clinical resolution of grade II-III acute GVHD. No subsequent chronic GVHD was observed in these patients. However, prolonged occurrence of host- specific Th-p was accompanied by clinically persisting acute GVHD and the onset of secondary chronic GVHD. In patients with no acute GVHD (grade 0) (n = 7) and grade I (n = 1) acute GVHD, host-specific Th-p were not detectable at all. We conclude that host-reactive Th are critically involved in the development and maintenance of acute GVHD and may contribute to the establishment of tolerance after genotypically HLA-identical sibling BMT.

scholarly journals Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1024-1030 ◽  
Author(s):  
D Weisdorf ◽  
R Haake ◽  
B Blazar ◽  
W Miller ◽  
P McGlave ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Acute Graft

Abstract We have analyzed the long term outcome of 197 patients who were treated for grade II to IV acute graft-versus-host disease (GVHD) following histocompatible allogeneic bone marrow transplantation (BMT). Of 469 recipients of sibling donor allografts performed at our center between January, 1979 and October, 1987, 197 patients (42%) developed greater than or equal to grade II acute GVHD at a median of 38 days (range 9 to 98 days) post-BMT. After treatment with corticosteroids (n = 160) or other immunosuppressive therapies (n = 37), 72 patients (41% +/- 8%; 95% confidence interval [CI]) achieved complete and continuing resolution of acute GVHD after a median of 21 days of therapy. Sixty- one patients required additional immunosuppressive therapy with high dose methylprednisolone, antithymocyte globulin (ATG)/steroids, or other therapies because of refractory or progressive symptoms of acute GVHD. Seven of these 61 patients eventually obtained complete and continuing remission after 13 to 57 days (median 50) of secondary treatment. The overall rate of chronic GVHD was 70% +/- 16%; 95% CI following grade II to IV acute GVHD. Twenty-five of the 197 patients never developed chronic GVHD, resulting in a Kaplan-Meier projection of 30% +/- 8% (95% CI) cure of moderate/severe acute GVHD. Analysis of clinical features associated with complete response (CR) to acute GVHD therapy identified more favorable responses to therapy in patients without either liver or skin involvement, patients with acute lymphoblastic leukemia, and donor/recipient pairs other than male patients with female donors. Older recipient age was not associated with more resistance to GVHD treatment. CR to GVHD treatment was associated with significantly better 5-year survival: 51% +/- 14% versus 32% +/- 11% for patients with therapy resistant acute GVHD (P = .004). GVHD was a major contributing cause of death in 49 of the 90 patients who died and was often complicated by infection or interstitial pneumonitis. Control of acute GVHD through immunosuppressive therapy did not affect the risk of leukemic relapse after transplantation.

scholarly journals Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 1024-1030 ◽  
Author(s):  
D Weisdorf ◽  
R Haake ◽  
B Blazar ◽  
W Miller ◽  
P McGlave ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Acute Graft

We have analyzed the long term outcome of 197 patients who were treated for grade II to IV acute graft-versus-host disease (GVHD) following histocompatible allogeneic bone marrow transplantation (BMT). Of 469 recipients of sibling donor allografts performed at our center between January, 1979 and October, 1987, 197 patients (42%) developed greater than or equal to grade II acute GVHD at a median of 38 days (range 9 to 98 days) post-BMT. After treatment with corticosteroids (n = 160) or other immunosuppressive therapies (n = 37), 72 patients (41% +/- 8%; 95% confidence interval [CI]) achieved complete and continuing resolution of acute GVHD after a median of 21 days of therapy. Sixty- one patients required additional immunosuppressive therapy with high dose methylprednisolone, antithymocyte globulin (ATG)/steroids, or other therapies because of refractory or progressive symptoms of acute GVHD. Seven of these 61 patients eventually obtained complete and continuing remission after 13 to 57 days (median 50) of secondary treatment. The overall rate of chronic GVHD was 70% +/- 16%; 95% CI following grade II to IV acute GVHD. Twenty-five of the 197 patients never developed chronic GVHD, resulting in a Kaplan-Meier projection of 30% +/- 8% (95% CI) cure of moderate/severe acute GVHD. Analysis of clinical features associated with complete response (CR) to acute GVHD therapy identified more favorable responses to therapy in patients without either liver or skin involvement, patients with acute lymphoblastic leukemia, and donor/recipient pairs other than male patients with female donors. Older recipient age was not associated with more resistance to GVHD treatment. CR to GVHD treatment was associated with significantly better 5-year survival: 51% +/- 14% versus 32% +/- 11% for patients with therapy resistant acute GVHD (P = .004). GVHD was a major contributing cause of death in 49 of the 90 patients who died and was often complicated by infection or interstitial pneumonitis. Control of acute GVHD through immunosuppressive therapy did not affect the risk of leukemic relapse after transplantation.

Infection Is the Major Cause of Mortality after Nonmyeloablative Unrelated Bone Marrow Transplantation with Alemtuzumab, Fludarabine and Melphalan.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5165-5165
Author(s):  
Michael P. Carroll ◽  
Diane BuchBarker ◽  
Rowena Schwartz ◽  
Mounzer E. Agha ◽  
Cheryl Tompkins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Cmv Reactivation ◽  
Acute Graft

Abstract Nonmyeloablative (NM) regimens for allogeneic (allo) hematopoietic cell transplantation (HCT) may be effective and associated with a low incidence of acute graft-versus-host disease (GVHD) in high-risk patients (pts) with hematologic malignancies. We report the results of NM bone marrow transplantation (BMT) from HLA-matched volunteer unrelated donors (VUDs) in 14 pts (median age 45 yr; range, 19–58 yr) with relapsed and/or refractory hematologic malignancies (1 ALL, 3 AML, 3 MDS/AML, 3 Hodgkin’s disease [HD], 2 multiple myeloma, 2 NHL). Thirteen pts had previous HCT: 10 autologous (auto), 1 related allo, 1 VUD, 1 auto and VUD. The NM regimen included alemtuzumab (20 mg/day x 5, days −8 through −4), fludarabine (30 mg/m2/day x 5, days −7 through −3) and melphalan (140 mg/m2 on day −2), as described by Kottaridis PD et al, Blood2000; 96: 2419 and Chakraverty R et al, Blood2002; 99: 1071. All pts received single-agent cyclosporine for prophylaxis of acute graft-versus-host disease (GVHD). Median doses of CD34+ and CD3+ cells were 2.79 (range, 1.35–4.87) x 106/kg and 2.8 (range, 1.99–6.39) x 107/kg, respectively. In 12 evaluable pts, median times to absolute neutrophils >0.5 x 109/L and platelets >20 x 109/L were 15 (range, 9–41) and 21 days (range, 15–41), respectively, after NMBMT. Two pts had primary graft failure (actuarial probability 16.4%; 95% confidence interval [CI], 0–37.6%). Two pts developed acute GVHD (1 grade I, 1 grade II) at 19 and 76 days, respectively, after NMBMT. The actuarial probability of all grades of acute GVHD is 16.1% (95% CI, 0–36.7%) and of grade II or greater GVHD is 9.1 % (95% CI, 0–26.2%). Two pts (1 with grade II acute GVHD) developed extensive chronic GVHD. Five pts developed cytomegalovirus (CMV) reactivation, for an actuarial probability of CMV reactivation of 58.5% (95% CI, 19.9–97.1%). One pt with CMV reactivation died with CMV infection at 122 days after NMBMT. Six pts died with other infections at a median of 74 days (range, 52–209) after NMBMT: 2 adenovirus (1 associated with graft failure), 2 toxoplasmosis, 1 Aspergillus (associated with graft failure), 1 Pseudomonas (associated with chronic GVHD). One pt died with pulmonary failure and chronic GVHD 267 days after NMBMT. Actuarial nonrelapse mortality (NRM) is 64.3% (95% CI, 35.5–93.1), and infection-associated mortality is 52.4% (95% CI 25.0–79.8%). Three pts (2 AML, 1 HD) relapsed at 181, 182 and 202 days, respectively, after NMBMT; actuarial relapse rate is 46.4% (95% CI, 26.4–66.4%). Three pts (1 ALL, 1 AML, 1 NHL) are alive without relapse at 164+, 184+ and 843+ days, respectively, after NMBMT; actuarial event-free survival (EFS) is 10.2% (95% CI, 0–28.8%). We conclude that opportunistic infection is the major cause of NRM after VUD NMBMT with a preparative regimen of alemtuzumab, fludarabine and melphalan and contributes significantly to the poor EFS in pts with relapsed/refractory hematologic malignancies thus treated. Efforts to improve immune reconstitution and infection prophylaxis after NMBMT with this regimen are warranted.

scholarly journals Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2252-2256 ◽  
Author(s):  
Y Morishima ◽  
Y Morishita ◽  
M Tanimoto ◽  
R Ohno ◽  
H Saito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Low Incidence ◽  
Acute Graft

Abstract Japanese patients with leukemia who received bone marrow from human leukocyte antigen (HLA)-compatible siblings had a low incidence of acute graft-versus-host disease (GVHD). Twenty-five (21%) of 120 patients developed moderate (grade II) to severe (grades III to IV) acute GVHD. Severe GVHD was only seen in patients older than 20 years of age. It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD. Thirteen (30%) of 44 patients receiving MTX alone and 10 (27%) of 37 patients receiving CSP alone developed grades II to IV acute GVHD. Multivariate life-table analysis indicated that the prophylaxis by MTX/CSP was the risk factor for the low incidence of grades II to IV acute GVHD. Compared with the reported incidence of acute GVHD in the patients of the United States, lower incidence of acute GVHD in Japanese BMT patients might be attributable to a lesser degree of genetic diversity in histocompatibility antigens among Japanese.

scholarly journals Low incidence of acute graft-versus-host disease by the administration of methotrexate and cyclosporine in Japanese leukemia patients after bone marrow transplantation from human leukocyte antigen compatible siblings; possible role of genetic homogeneity. The Nagoya Bone Marrow Transplantation Group

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2252-2256 ◽  
Author(s):  
Y Morishima ◽  
Y Morishita ◽  
M Tanimoto ◽  
R Ohno ◽  
H Saito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Low Incidence ◽  
Acute Graft

Japanese patients with leukemia who received bone marrow from human leukocyte antigen (HLA)-compatible siblings had a low incidence of acute graft-versus-host disease (GVHD). Twenty-five (21%) of 120 patients developed moderate (grade II) to severe (grades III to IV) acute GVHD. Severe GVHD was only seen in patients older than 20 years of age. It is also notable that only 2 (5%) of 39 patients who received the combination of methotrexate and cyclosporine (MTX/CSP) for the prevention of GVHD developed grade II acute GVHD, and none developed grades III to IV acute GVHD. Thirteen (30%) of 44 patients receiving MTX alone and 10 (27%) of 37 patients receiving CSP alone developed grades II to IV acute GVHD. Multivariate life-table analysis indicated that the prophylaxis by MTX/CSP was the risk factor for the low incidence of grades II to IV acute GVHD. Compared with the reported incidence of acute GVHD in the patients of the United States, lower incidence of acute GVHD in Japanese BMT patients might be attributable to a lesser degree of genetic diversity in histocompatibility antigens among Japanese.

A Single Nucleotide Polymorphism in the NLRP3 Gene Is Associated with Acute Graft-Versus-Host Disease After HLA-Matched Unrelated Bone Marrow Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4073-4073
Author(s):  
Luis J. Espinoza ◽  
Akiyoshi Takami ◽  
Katsuya Nakata ◽  
Makoto Onizuka ◽  
Takakazu Kawase ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Nucleotide Polymorphism ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Nlrp3 Gene ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Abstract 4073 NOD-like receptor family, pyrin domain containing 3 (NLRP3) is an innate immune receptor that exerts functions in the regulation of inflammation and apoptosis. Recent studies have shown that the single nucleotide polymorphism (SNP) rs10754558 (C>G) at the 3' untranslated region of NLRP3 gene is functional and is associated with various immunological diseases. Allele G is linked with a higher activity of NLRP3 than allele A, and plays important roles in increased susceptibility to allergic reactions and in protection of HIV infection. This study retrospectively examined the impact of the NLRP3 genotype of a total 659 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in unrelated HLA 12/12 matched bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The genotype frequencies of G/G, G/C and C/C were 19%, 50% and 31% in recipients and 18%, 49% and 32% in donors (P =0.79). The donor G/G or G/C genotype was associated with a significantly higher incidence of grades III to IV acute graft-versus-host disease (GVHD; 15% vs. 7%, P =0.004; Fig 1B) and a trend toward a higher incidence of grades II to IV acute GVHD (34% vs. 27%, P =0.06; Fig 1A), while no significant differences between the G/G genotype and G/C genotype were seen. The donor G/G or G/C genotype remained statistically significant in the multivariate analysis for the development of grades III to IV acute GVHD (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.22 to 3.90; P =0.009) as well as a trend toward an association with grades II-IV acute GVHD (HR, 1.31; 95% CI, 0.96 to 1.80; P =0.09). The recipient NLRP3 genotype did not significantly influence the transplant outcomes. These results suggest an association of the donor NLRP3 genotype with the development of acute GVHD after unrelated BMT. Genotyping for the NLRP3 rs10754558 could be useful in donor selection and risk-adapted management of transplanted patients, and may furthermore offer some novel therapeutic insights into the mechanisms of acute GVHD. Disclosures: No relevant conflicts of interest to declare.

Reduction in the Incidence and Severity of Graft Versus Host Disease in HLA-Matched and Haploidentical Bone Marrow Transplantation Using Posttrasplant Cyclophosphamide. Experience of Two Latino-American Institutions

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5880-5880
Author(s):  
Roberto Ovilla ◽  
Uendy Perez-Lozano ◽  
Dannia Calles-Payan ◽  
Lucia A Reynolds-Ocampo ◽  
Gabriela Ruiz-Reyes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
High Dose ◽  
Host Disease ◽  
Graft Versus Host

Abstract The Graft Versus Host Disease (GVHD) grades II-IV is present in up to 40% in Human Leucocyte Antigen (HLA) - identical related transplants and up to 80% of non-related. The HLA-haploidentical bone marrow transplantation (BMT) has been associated with significant risks of graft rejection and severe GVHD, as an excessive alloreactivity by host and donor T cells. High dose of Cyclofosfamide (Cy) after BMT inhibits both graft rejection and GVHD. We want to share our experience in preventing GVHD in HLA - haploidentical alloBMT and HLA-matched related BMT using the strategy of Cy post-Transplant. We evaluated 25 patients from March 2013 to June 2014, all of them were in advanced stages of the disease or they have characteristics of poor prognosis before transplantation. All patients received non-myeloablative conditioning and Cyclofosfamide (Cy) 50 mg/Kg postrasplant (on days 3 and 4 after transplantation), Mycophenolate mofetil (from day 5 to 35) and Tacrolimus (from day 5 to 180). The 64% (16) were male, mean age 30.6 years (range 2 – 67 years), with a average follow-up of 198 days (range 14-512 days). The 76% (19) were HLA-matched related alloBMT (7 patients) and HLA-haploidentical alloBMT (12 patients) in hematological malignancies, the rest of trasplants (24%) were HLA-haploidentical alloBMT in benign hematological diseases, overall survival (OS) at day 180 by type of transplant was 70%, 64%, and 67% respectively. 28% (7) had graft failure. 11 patients had no acute GVHD, 10 patients had GVHD grade I-II, and 3 patients had grade III, only 1 patient died because of grade IV (P = 0.005). Chronic GVHD occurred in 4 patients (16%). As a complication related to Cy therapy, hemorrhagic cystitis was observed 32%(8). Posttransplantation cyclophosphamide is able to reduce the likelihood of developing chronic GVHD and reduces the severity of acute GVHD, it plays an important role in the feasibility of a haploidentical transplant because the lower incidence of GVHD. Our results showed one of the most satisfactory and encouraging studies on the use of post-transplantation Cy performed in Latin America. Disclosures No relevant conflicts of interest to declare.

Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2434-2439 ◽  
Author(s):  
Nobuhiro Tsukada ◽  
Hisaya Akiba ◽  
Tetsuji Kobata ◽  
Yoshifusa Aizawa ◽  
Hideo Yagita ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Murine Model ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Graft Versus Host ◽  
Acute Graft

Expression of CD134 (OX40) on activated CD4+ T cells has been observed in acute graft-versus-host disease (GVHD) after human and rat allogeneic bone marrow transplantation (BMT). We investigated the role of interaction between CD134 and CD134 ligand (CD134L) in a murine model of acute GVHD by using a newly established monoclonal antibody (mAb) against murine CD134L. Acute GVHD was induced by transfer of bone marrow cells and spleen cells into lethally irradiated recipients in a parent (C57BL/6) to first filial generation (C57BL/6 crossed with DBA/2) BMT. Administration of anti-CD134L mAb significantly reduced the lethality of acute GVHD and other manifestations of the disease, such as loss of body weight, hunched posture, diarrhea, and patchy alopecia. The survival rate 80 days after BMT in mice treated with the mAb was about 70%, whereas all mice treated with control antibodies died within 43 days. Histologic examinations revealed that inflammatory changes in target organs such as the liver, gut, and skin were also ameliorated in mice treated with the mAb compared with control mice. An in vitro assay of T-cell proliferation showed a marked hyporesponsiveness to host alloantigen in samples from mice treated with anti-CD134L mAb. In addition, low levels of interferon γ and transiently elevated levels of interleukin 4 and IgE in serum samples were found in mice treated with anti-CD134L mAb. These results suggest that CD134-CD134L interactions have an important role in the pathogenesis of acute GVHD.

Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2434-2439 ◽  
Author(s):  
Nobuhiro Tsukada ◽  
Hisaya Akiba ◽  
Tetsuji Kobata ◽  
Yoshifusa Aizawa ◽  
Hideo Yagita ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Graft Versus Host Disease ◽  
Murine Model ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Expression of CD134 (OX40) on activated CD4+ T cells has been observed in acute graft-versus-host disease (GVHD) after human and rat allogeneic bone marrow transplantation (BMT). We investigated the role of interaction between CD134 and CD134 ligand (CD134L) in a murine model of acute GVHD by using a newly established monoclonal antibody (mAb) against murine CD134L. Acute GVHD was induced by transfer of bone marrow cells and spleen cells into lethally irradiated recipients in a parent (C57BL/6) to first filial generation (C57BL/6 crossed with DBA/2) BMT. Administration of anti-CD134L mAb significantly reduced the lethality of acute GVHD and other manifestations of the disease, such as loss of body weight, hunched posture, diarrhea, and patchy alopecia. The survival rate 80 days after BMT in mice treated with the mAb was about 70%, whereas all mice treated with control antibodies died within 43 days. Histologic examinations revealed that inflammatory changes in target organs such as the liver, gut, and skin were also ameliorated in mice treated with the mAb compared with control mice. An in vitro assay of T-cell proliferation showed a marked hyporesponsiveness to host alloantigen in samples from mice treated with anti-CD134L mAb. In addition, low levels of interferon γ and transiently elevated levels of interleukin 4 and IgE in serum samples were found in mice treated with anti-CD134L mAb. These results suggest that CD134-CD134L interactions have an important role in the pathogenesis of acute GVHD.

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