This work was supported by the Italian Ministry of Health, Rome (Finalized Project 2008-2011, Establishment of a GMP validated Biobank; AIDS Project 2009, 40H.87, HIV T and B epitope mapping) and by EU, Bruxelles (Grant LSHB-CT-2005-018680). GLP was supported by EU FP7 program GA 242146.
TRANSPLANTATION AND CELLULAR ENGINEERING
A registry of HLA-typed donors for production of virus-specific CD4 and CD8 T lymphocytes for adoptive reconstitution of immune-compromised patients
Article first published online: 20 JUL 2014
© 2014 AABB
Volume 54, Issue 12, pages 3145–3154, December 2014
How to Cite
Li Pira, G., Ivaldi, F., Starc, N., Landi, F., Rutella, S., Locatelli, F., Sacchi, N., Tripodi, G. and Manca, F. (2014), A registry of HLA-typed donors for production of virus-specific CD4 and CD8 T lymphocytes for adoptive reconstitution of immune-compromised patients. Transfusion, 54: 3145–3154. doi: 10.1111/trf.12754
- Issue published online: 11 DEC 2014
- Article first published online: 20 JUL 2014
- Manuscript Accepted: 6 MAY 2014
- Manuscript Revised: 5 MAY 2014
- Manuscript Received: 20 MAR 2014
- Italian Ministry of Health, Rome
- EU, Bruxelles. Grant Number: LSHB-CT-2005-018680
- EU FP7 program. Grant Number: GA 242146
Virus-specific CD4 and CD8 T lymphocytes from HLA-matched donors are effective for treatment and prophylaxis of viral infections in immune-compromised recipients of hematopoietic stem cell transplant recipients. Adoptive immune reconstitution is based on selection of specific T cells or on generation of specific T-cell lines from the graft donor. Unfortunately, the graft donor is not always immune to the relevant pathogen or the graft donor may not be available (registry-derived or cord blood donors).
Study Design and Methods
Since the possibility of using T cells from a third-party subject is now established, we screened potential donors for T-cell responses against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus, the viruses most frequently targeted by adoptive immune reconstitution. Specific T-cell responses against viral antigens were analyzed in 111 donors using a miniaturized interferon-γ release assay.
Responders to CMV were 64%, to EBV 40%, and to adenovirus 51%. Simultaneous responders to the three viruses were 49%. CMV-specific CD4 and CD8 T-cell lines could be generated from 11 of 12 donors defined as positive responders according to the T-cell assay.
These data demonstrate that a large fraction of volunteers can be recruited in a donor registry for selection or expansion of virus specific T cells and that our T-cell assay predicts the donors' ability to give rise to established T-cell lines endowed with proliferative potential and effector function for adoptive immune reconstitution.