NDLI: Cognate CD4 T-Cell Licensing of Dendritic Cells Heralds Anti-Cytomegalovirus CD8 T-Cell Immunity after Human Allogeneic Umbilical Cord Blood Transplantation

Content Provider	PubMed Central
Author	Flinsenberg, T. W. H. Spel, L. Jansen, M. Koning, D. Haar, C. De Plantinga, M. Scholman, R. Loenen, M. M. Van Nierkens, S. Boon, L. Baarle, D. Van Heemskerk, M. H. M. Boelens, J. J. Boes, M.
Editor	Frueh, K.
Copyright Year	2015
Abstract	Reactivation of human cytomegalovirus (CMV) is hazardous to patients undergoing allogeneic cord blood transplantation (CBT), lowering survival rates by approximately 25%. While antiviral treatment ameliorates viremia, complete viral control requires CD8+ T-cell-driven immunity. Mouse studies suggest that cognate antigen-specific CD4+ T-cell licensing of dendritic cells (DCs) is required to generate effective CD8+ T-cell responses. For humans, this was not fully understood. We here show that CD4+ T cells are essential for licensing of human DCs to generate effector and memory CD8+ T-cell immunity against CMV in CBT patients. First, we show in CBT recipients that clonal expansion of CMV-pp65-specific CD4+ T cells precedes the rise in CMV-pp65-specific CD8+ T cells. Second, the elicitation of CMV-pp65-specific CD8+ T cells from rare naive precursors in cord blood requires DC licensing by cognate CMV-pp65-specific CD4+ T cells. Finally, also CD8+ T-cell memory responses require CD4+ T-cell-mediated licensing of DCs in our system, by secretion of gamma interferon (IFN-γ) by pp65-specific CD4+ T cells. Together, these data show that human DCs require licensing by cognate antigen-specific CD4+ T cells to elicit effective CD8+ T-cell-mediated immunity and fight off viral reactivation in CBT patients.
Related Links	http://dx.doi.org/10.1128/jvi.01850-14
Ending Page	1069
Page Count	12
Starting Page	1058
File Format	PDF
ISSN	0022538X
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	2
Volume Number	89
Language	English
Publisher	American Society for Microbiology
Publisher Date	2015-01-15
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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