Adoptive Immunotherapy for Interstitial Pneumonia Associated with Cytomegalovirus Infection

Numazaki, Kei; Ikehata, Masami; Yanai, Seika; Umetsu, Masao; Motoya, Hisashi; Chiba, Shunzo; Sekine, Teruaki

doi:10.1086/516959

Cited by 9 publications

(6 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…T cells were prepared as described previously (16–18). Briefly, the mononuclear cells were separated from transplanted cord blood residua, and purifying with CD4 monoclonal antibody (mAb)‐coated magnetic beads (Dynal Biotech, Oslo, Norway), CD4‐positive cells were cultured for 1 wk in the presence of recombinant IL‐2 (350 IU/mL; Proleukin, Chiron B.V, Amsterdam, the Netherlands) in a flask with immobilized anti‐CD3 mAb, OKT3 (5 μ g/mL; Janssen‐Kyowa, Tokyo, Japan).…”

Section: Preparation Of Donor Cord Blood‐derived Activated T Cells Fomentioning

confidence: 99%

Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome

Tomizawa

Aoki

Nagasawa

et al. 2005

European J of Haematology

Self Cite

View full text Add to dashboard Cite

Omenn syndrome is a variant form of severe combined immunodeficiency. It is fatal unless treated by allogeneic stem cell transplantation (SCT), which is the only curative approach. However, both treatment-related complications and graft rejection are major obstacles to treatment success. This report describes a case with Omenn syndrome who developed mixed chimerism after unrelated cord blood transplantation (UCBT). This case was successfully treated by altering the patient's immunosuppression and donor lymphocyte infusion (DLI) with donor cord blood-derived activated CD4+ T cells ex vivo expanded from the cord blood cell residues in an infused bag. This novel development to expand CD4+ T-lymphocytes from the donor cord blood unit for the use of DLI would serve as a useful method to overcome the risk of graft rejection in SCT for primary immunodeficiency disorders with residual cell-mediated immunity without compounding graft-vs.-host disease, especially in the UCBT setting.

show abstract

Section: Preparation Of Donor Cord Blood‐derived Activated T Cells Fomentioning

confidence: 99%

Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome

Tomizawa

Aoki

Nagasawa

et al. 2005

European J of Haematology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The efficacy and clinical applicability of adoptive immunotherapy have been demonstrated in several clinical studies. The transfer of cytomegalovirus (CMV)-specific T cells has been used to safely and successfully protect against CMV reactivation in myelodepleted bone marrow transplant patients, as well as to eliminate active viral disease in immunosuppressed patients Walter et al, 1995;Numazaki et al, 1997). Moreover, AIT has proven to be highly effective against Epstein-Barr virus-associated lymphoproliferative disease and lymphoma (Rooney et al, 1998;Gottschalk et al, 2005;Cho et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Selective Modification of Antigen-Specific T Cells by RNA Electroporation

et al. 2008

View full text Add to dashboard Cite

It has been observed that the efficient transfection of T cells by RNA electroporation requires prior activation of T cells with mitogens or by anti-CD3 antibody stimulation. We hypothesized that this requirement for T cell activation could be leveraged to express marker genes within activated T cells responding to antigen-pulsed dendritic cells and allow for the selective enrichment and modification of antigen-specific T cells. Using electroporation of mRNA encoding green fluorescent protein as a marker gene, we demonstrate that RNA electroporation can efficiently allow for the separation of cytomegalovirus-specific CD8+ and CD4+ T cells from bulk culture responding to cytomegalovirus pp65 antigen-pulsed dendritic cells. Furthermore, we demonstrate that cytomegalovirus-specific T cells can be functionally modified by RNA transfection of the C-X-C chemokine receptor, CXCR2, to migrate efficiently toward a variety of CXCR2-specific chemokines in vitro and in vivo. These studies demonstrate the utility of RNA transfection as a simple method by which to purify and selectively modify the function of antigen-specific T cells for use in adoptive immunotherapy, and importantly provide evidence that transient expression of proteins by RNA transfection is an efficient means of modulating the in vivo function of activated T cells.

show abstract

“…However, there are sporadic published cases in which established CMV-P, refractory to antiviral treatment, responded to a leukocyte infusion from a CMV seropositive donor in one case, 14 and to an autologous, expanded T cell infusion in another. 15 In neither of these cases was there a significant deterioration of the pneumonitis.…”

Section: The Cytopathological Hypothesismentioning

confidence: 91%

Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited

Barry

Jánossy

2000

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Various hypotheses have been proposed to explain why cytomegalovirus pneumonitis (CMV-P) is frequent and severe in bone marrow transplant patients while remaining rare and mild in HIV infected patients. One hypothesis suggests that CMV-P is an immunopathological condition that is common in bone marrow transplantation (BMT) under the effects of an abnormally regenerating immune system that reacts against CMV infected lung tissue. Such a hypothesis implicates CD4 T lymphocytes as one of the critical cell populations involved in immunopathology and also suggests that this process would be aborted by CD4 T cell deficiency in HIV infection. However, studies correlating the onset of CMV-P with lymphocyte reconstitution following BMT have revealed that CD4 cells are present at very low frequencies in the blood during the early period after transplantation when most cases of CMV-P occur. Furthermore, studies directly investigating bronchoalveolar lavage cell types during episodes of CMV-P in BMT patients have also failed to demonstrate significant CD4 involvement and, instead, have emphasized a predominance of natural killer (NK) cells and CD8 cells. These findings serve as the basis for questioning the validity of a CD4-driven immunopathological model of CMV-P in BMT. On the other hand, a variety of experimental and clinical observations support the protective role of CMV-specific CD3 + CD8 T lymphocytes against CMV in both immunocompetent individuals and BMT patients. In a murine BMT model, adoptive transfer of syngeneic BM cells was associated with massive increases in lung CD8 cells which resulted in the resolution rather than the exacerbation of existing CMV-P. In the light of these findings a more plausible hypothesis for CMV-P in BMT is that during the early period after transplantation adequate protective CD8 responses are absent and an uncontrolled CMV proliferation is allowed to develop. Once a critical viral load is reached a cytokine 'storm' may be triggered in the lung tissue that aggravates direct CMV-associated cytopathic

show abstract

Adoptive Immunotherapy for Interstitial Pneumonia Associated with Cytomegalovirus Infection

Cited by 9 publications

References 1 publication

Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome

Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome

Selective Modification of Antigen-Specific T Cells by RNA Electroporation

Cytopathology or immunopathology? The puzzle of cytomegalovirus pneumonitis revisited

Contact Info

Product

Resources

About