scholarly journals Extracorporeal Photopheresis Attenuates Murine Graft-versus-Host Disease via Bone Marrow–Derived Interleukin-10 and Preserves Responses to Dendritic Cell Vaccination

2011 ◽  
Vol 17 (6) ◽  
pp. 790-799 ◽  
Author(s):  
Christian M. Capitini ◽  
Jessica P.E. Davis ◽  
Shannon M. Larabee ◽  
Sarah Herby ◽  
Nicole M. Nasholm ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cell ◽  
Graft Versus Host Disease ◽  
Interleukin 10 ◽  
Dendritic Cell Vaccination ◽  
Extracorporeal Photopheresis ◽  
Host Disease ◽  
Graft Versus Host

BB02 Improves Therapeutical Effectiveness Of Extracorporeal Photopheresis With 8-MOP In a Murine Model Of Graft-Versus-Host Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5416-5416
Author(s):  
David Garcia-Bernal ◽  
Miguel Blanquer ◽  
Jose Antonio del Rio ◽  
Enrique Correal ◽  
Maria del Carmen Algueró ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Murine Model ◽  
Lethal Dose ◽  
Therapeutic Effectiveness ◽  
Allogeneic Bone ◽  
Extracorporeal Photopheresis ◽  
Host Disease ◽  
Graft Versus Host

Abstract Introduction Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory therapy involving the separation of peripheral blood autologous mononuclear cells followed by ex-vivo administration of 8-methoxypsoralen (8-MOP) and UVA radiation before reinfusion. ECP is efficient for the treatment of multiple diseases mediated by unregulated T cell populations, such as cutaneous T cell lymphoma, autoinmune diseases or graft-versus-host disease (GVHD), the major complication after allogeneic bone marrow transplantation. Our aim in the present work was to compare the therapeutic effectiveness of 8-MOP with other two new compounds (BB01 and BB02) in a experimental murine model of GVHD. Methods Murine GVHD was induced after transplanting bone marrow cells and splenocytes from donor Balb/c mice into C57Bl6J recipients previously conditioned with a lethal dose of 10 Gy split into two doses of 5 Gy spaced 24 hours apart. To investigate the therapeutic effectiveness of ECP with either 8-MOP, BB01 or BB02, splenocytes from separate cohorts of C57Bl6J with GVHD were isolated 12 days after transplantation, incubated with the different compounds, irradiated with UVA light and injected intravenously once a week for four weeks. Survival after transplantation was monitored daily and clinical GVHD was graded using a previously described score analyzing weight loss, posture (hunching), activity, skin integrity and fur texture (Cooke et al, 1996). Mice of each group were evaluated and graded from 0 to 2 for each criterion, obtaining a clinical index by summation of the five criteria scores (maximum index=10). Results Mice treated weekly with BB02 showed a significant higher survival than those treated with 8-MOP (p=0,038), while BB01 had a similar effect to that of 8-MOP. Mice treated with either compound improved their clinical GVHD score compared to untreated mice group, being significantly lower with BB02 than with BB01 and 8-MOP (p=0,023). Conclusions BB02 was more efficient than 8-MOP in the reversal of murine GVHD, while BB01 showed the same therapeutic effectiveness than 8-MOP. Acknowledgments Work financed by the Spanish Ministry of Science and Innovation (Ref: BFU2010-19599) and the Spanish Net of Cell Therapy (TerCel) from Institute of Health Carlos III. Disclosures: No relevant conflicts of interest to declare.

Extracorporeal Photopheresis Diminishes Graft-Versus-Host-Disease and Modulates Dendritic Cell Cytokine Production.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2177-2177
Author(s):  
Jessica P. Davis ◽  
Sarah Herby ◽  
Meghaan P. Walsh ◽  
Christian M. Capitini ◽  
Martin Guimond ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Weight Loss ◽  
Lymph Node ◽  
Graft Versus Host Disease ◽  
Cytokine Production ◽  
Extracorporeal Photopheresis ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Uva Light

Abstract Background: Graft-versus-host disease (GVHD) remains one of the largest obstacles in allogeneic stem cell transplantation. Current therapies for GVHD generally involve systemic immunosuppression resulting in increased risk of infection and relapse. Extracorporeal Photopheresis (ECP) is an emerging therapy for chronic GVHD that offers the potential of selective immunomodulation. In ECP, patient leukocytes are treated with 8-methoxypsoralen (8-MOP) and UVA light, causing them to undergo apoptosis, and are re-infused into the patient. Because ECP has been studied mostly in the clinical setting, however, the mechanism by which this infusion of apoptotic cells impacts GVHD remains unclear. We hypothesized that ECP-treated cells interact with recipient dendritic cells (DCs) to induce tolerance. We applied ECP to a murine GVHD model and explored the effects of ECP-treated cells on DCs. Methods: ECP: Splenocytes were incubated with 8-MOP at 200 ng/ml and exposed to UVA light (5 J/cm2). Bone Marrow Transplant (BMT): C3H.SW mice were irradiated (1000 cGy) and given 10 × 106bone marrow and 5 ×106 lymph node C57BL/6 (B6) cells on day 0. 10 ×106 ECP-treated splenocytes were administered on day 1. Co-culture: Female B6 BM-derived DCs were cultured for 7 days with GM-SCF and IL-4 and incubated overnight with untreated, irradiated (3000 cGy) or ECP-treated splenocytes. Anti-CD40 was used to activate DCs. DC phenotype and cytokine production were examined using flow cytometry. Vaccine: Male B6 DCs were co-incubated with untreated, irradiated or ECP-treated female B6 splenocytes and injected into naive female B6 recipients on days 14 and 28. On day 42, responses against the male histocompatibility antigen complex (H-Y) were assayed using IFN-gamma ELISPOT. Results: 85–94% of ECP-treated cells were Annexin+/7AAD+ 24 hours after ECP treatment. Infusion of ECP-treated cells diminished GVHD-associated weight loss regardless of the strain of the ECP donor (Fig. 1) and restored responsiveness to H-Y vaccination. In co-culture experiments, the presence of ECP-treated cells did not alter phenotypic maturation of DCs. However, co-culture of DCs with ECP-treated cells did alter DC cytokine production resulting in less IL-12 production when compared to anti-CD40 alone (1.0% vs. 4.2% of CD11b+/CD11c+ cells). Finally, immunization of naive female mice with male DCs co-cultured with ECP-treated cells resulted in a modest but statistically significant (p=.0499) decrease in subdominant, class I H-Y responses compared to DCs incubated with untreated splenocytes. Conclusion: The administration of ECP-treated cells in vivo appears to lessen the severity of GVHD, allowing mice to maintain immunocompetence. DCs cultured in the presence of ECP-treated cells can mature phenotypically but exhibit altered cytokine production. Activated, co-incubated DCs are less potent when used as a vaccine. This data suggests that perhaps the alteration of recipient DCs may contribute to the beneficial effect of ECP in GVHD. Ongoing experiments continue to explore the role of recipient DCs in ECP treatment of GVHD. Figure 1. Female C3.HSW mice were lethally irradiated and received 10 × 106 bone marrow and 5 × 106 lymph node C57BL/6 (B6) cells on Day 0. On Day 1, 10 × 106 ECP-treated cells from either recipient (C3.HSW), donor (B6) or 3rd Party (BALB.B) mice were administered. Weight loss was monitored twice weekly. Figure 1. Female C3.HSW mice were lethally irradiated and received 10 × 106 bone marrow and 5 × 106 lymph node C57BL/6 (B6) cells on Day 0. On Day 1, 10 × 106 ECP-treated cells from either recipient (C3.HSW), donor (B6) or 3rd Party (BALB.B) mice were administered. Weight loss was monitored twice weekly.

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