CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo

50 Scopus citations

Abstract

Adoptive transfer of cytomegalovirus (CMV)-specific T cells derived from adult seropositive donors can effectively restore antiviral immunity after transplantation. However, CMV-seronegative donors lack CMV-specific memory T cells, which restricts the availability of virus-specific T cells for immunoprophylaxis. We demonstrate the feasibility of deriving CMV-specific T cells from naïve cells for T cell therapy. Naïve T cells primed to recognize CMV were restricted to different, atypical epitopes than T cells derived from CMV-seropositive individuals; however, these two cell populations had similar avidities. CMV-seropositive individuals also had T cells recognizing these atypical epitopes, but these cells had a lower avidity than those derived from the seronegative subjects, which suggests that high-avidity T cells to these epitopes may be lost over time. Indeed, recipients of cord blood (CB) grafts who did not develop CMV were found by clonotypic analysis to have T cells recognizing atypical CMVpp65 epitopes. Therefore, we examined unmanipulated CB units and found that T cells with T cell receptors restricted by atypical epitopes were the most common, which may explain why these T cells expanded. When infused to recipients, naïve donor-derived virus-specific T cells that recognized atypical epitopes were associated with prolonged periods of CMV-free survival and complete remission. These data suggest that naïve-derived T cells from seronegative patients may be an additional source of cells for CMV immunoprophylaxis.

Original languageEnglish (US)
Article number285ra63
JournalScience translational medicine
Volume7
Issue number285
DOIs
StatePublished - Apr 29 2015

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hanley, P. J., Melenhorst, J. J., Nikiforow, S., Scheinberg, P., Blaney, J. W., Demmler-Harrison, G., Cruz, C. R., Lam, S., Krance, R. A., Leung, K. S., Martinez, C. A., Liu, H., Douek, D. C., Heslop, H. E., Rooney, C. M., Shpall, E. J., Barrett, A. J., & Bollard, C. M. (2015). CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo. Science translational medicine, 7(285), [285ra63]. https://doi.org/10.1126/scitranslmed.aaa2546