Dendritic cell vaccination in an allogeneic stem cell recipient receiving a transplant from a human cytomegalovirus (HCMV)-seronegative donor: induction of a HCMV-specific T(helper) cell response.
OBJECTIVE
In the absence of a protective immune response, human cytomegalovirus (HCMV) infection remains a life-threatening complication after allogeneic stem cell transplantation (SCT), especially in recipients of grafts from HCMV-seronegative donors. After allogeneic SCT from a seronegative donor, prolonged and severe immune deficiency often leads to infectious complications. Vaccination with antigen-loaded dendritic cells (DC) has been shown to be a potent approach for the induction of antigen-specific cytotoxic T-cell responses in vivo. For protection from subsequent HCMV reactivation, a sustained immune response is necessary, including antigen-specific CD4(+) T cells.


METHODS
We report the case of an 18-year-old girl with high-risk acute lymphoblastic leukemia that received an allogeneic SCT in CR2. After an HCMV infection, the graft was rejected and she received a second transplant from an HLA-mismatched, HCMV-seronegative family donor. She was treated with pp65-pulsed monocyte-derived DC at day 200 post-SCT, using a recombinant pp65 protein. Until day 200 post-SCT, HCMV reactivated six times with emerging viral resistance to antiviral chemotherapy.


RESULTS
After vaccination with protein-pulsed DC, an induction and expansion of HCMV-specific T(helper) cells and cytotoxic T lymphocytes was observed, associated with a sustained clearance of the HCMV viremia. Antiviral treatment could be tapered without recurrence of viremia within the first year post-SCT.


CONCLUSIONS
pp65-pulsed DC could induce antigen-specific T-cell responses even after a SCT from an HCMV-seronegative donor. After vaccination with pp65-pulsed DC, a sustained antigen-specific T-cell response prevented concurrent HCMV viremia. Emergence of antigen-specific T(helper) cells may be essential for a sustained, functional T-cell response post-SCT.
Feuchtinger
Tobias
T
Department of Pediatric Hematology/Oncology, University Children's Hospital, Eberhard-Karls University, Tübingen, Germany. tobias.feuchtinger@med.uni-tuebingen.de
Opherk
Kathrin
K
Bicanic
Oliver
O
Schumm
Michael
M
Grigoleit
Götz Ulrich
GU
Hamprecht
Klaus
K
Jahn
Gerhard
G
Handgretinger
Rupert
R
Lang
Peter
P
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000276:immunology; D033581:Stem Cell Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014019:Tissue Donors; D014611:Vaccination; D014763:Viral Matrix Proteins / Q000276:immunology; D014766:Viremia / Q000517:prevention & control
D000914:Antibodies, Viral; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa